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Wang K, Zhang L, Li Q, Xu S, Wang P, Shi H, Zhang Y, Li J. The effect of PM 2.5 exposure on placenta and its associated metabolites: A birth cohort study. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 292:117891. [PMID: 39978100 DOI: 10.1016/j.ecoenv.2025.117891] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/22/2024] [Revised: 01/24/2025] [Accepted: 02/10/2025] [Indexed: 02/22/2025]
Abstract
The placenta is an important organ for fetal growth. Air pollution during pregnancy may cause adverse effects on offsprings via placental dysfunction. However, the metabolites underlie the effects of PM2.5 on placenta have not been well studied. 329 pregnant women were randomly selected from the Shanghai Maternal-Child Pairs Cohort. Gestational PM2.5 exposure levels were assessed using individual air sampling method and satellite-based exposure assessment mode, respectively. Placental weight, length, width and thickness were measured by obstetrician-gynecologist at the time of delivery. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to quantify metabolites in serum from the first and third trimester. Associations between PM2.5 and placental characteristics were analyzed by generalized estimating equation and multiple linear regression. The exposure-response relationship was plotted using restricted cubic splines (RCS). Based on the meet-in-the-middle approach, the metabolites underlying the effects of PM2.5 on placenta were explored. The associations between placental width (βTrimester2=-0.497, 95 %CI: -0.801, -0.193), (βTrimester3=-0.279, 95 % CI: -0.543, -0.016) and chorionic disk area (βTrimester2=-12.634,95 %CI: -21.698, -3.570), (βTrimester3=-9.113, 95 %CI: -17.113, -1.112) with PM2.5 exposure at the second and third trimester were found. The associations between placental characteristics with PM2.5 exposure assessed by individual air sampling and satellite-based methods were consistent. L-arginine (L-Arg), caprylic acid (CA), tauroursodeoxycholic acid (TUDCA), glycylproline (Gly-Pro), maltotriose (MT) and N-acetylneuramic acid (NANA) intermediate the effect of PM2.5 exposure on placental chorionic disk area in the third trimester. CONCLUSION: The second and third trimesters may be the sensitive windows of placental abnormalities to PM2.5 exposure. Caprylic acid (CA), glycylproline (Gly-Pro), and N-acetylneuramic acid (NANA) play a key role on the effects of PM2.5 exposure on placenta. This study provides potential biomarkers of placental exposure to PM2.5, providing an opportunity for future research as well as detection.
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Affiliation(s)
- Kuancheng Wang
- Key Laboratory of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Liyi Zhang
- Key Laboratory of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Qiang Li
- Putuo District Center for Disease Control & Prevention, Shanghai 200333, China
| | - Siqi Xu
- Putuo District Center for Disease Control & Prevention, Shanghai 200333, China
| | - Pengpeng Wang
- Department of Occupational and Environmental Health, College of Public Health, Zhengzhou University, Zhengzhou 450001, China
| | - Huijing Shi
- Key Laboratory of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China
| | - Yunhui Zhang
- Key Laboratory of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
| | - Jiufeng Li
- Key Laboratory of Health Technology Assessment, National Health Commission of the People's Republic of China, Fudan University, Shanghai 200032, China; Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai 200032, China.
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Zhang Y, Chen Q, Wang L, Geng H, Zhu Z, Lv C, Zhao Y, Wang X, Sun C, Chen P, Zhang C. Spatially-resolved characterization of the metabolic and N-glycan alterations in colorectal cancer using matrix-assisted laser desorption/ionization mass spectrometry imaging. RSC Adv 2025; 15:1838-1845. [PMID: 39839237 PMCID: PMC11747861 DOI: 10.1039/d4ra08100e] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 01/10/2025] [Indexed: 01/23/2025] Open
Abstract
Colorectal cancer is the second leading cause of cancer-related deaths worldwide, and its development typically involves complex metabolic reprogramming. By mapping the spatial distributions of metabolites and N-glycans in heterogeneous colorectal cancer tissues, we can elucidate cancer-associated metabolic and N-glycan changes. Herein, we combine mass spectrometry imaging-based metabolomics and N-glycomics to characterize the spatially resolved reprogramming of metabolites and N-glycans in colorectal cancer tissues. The metabolic characteristics of different regions of colorectal cancer were evaluated through the utilization of orthogonal partial least squares discriminant analysis. In combination with metabolic pathway enrichment analysis, significant alterations were identified in the fatty acid metabolism, arginine and proline metabolism of colorectal cancer. Cancer cell regions exhibited a marked upregulation of saturated fatty acids, monounsaturated fatty acids, polyamines, and histidine. Additionally, we discovered that the high-mannose N-glycans were predominantly distributed in tumor tissue regions, whereas complex N-glycans were more commonly found in the normal tissue regions adjacent to the tumor. Such findings provide new insights into the spatial signatures of metabolites and N-glycans in colorectal cancer, thereby offering a crucial basis for the diagnosis of colorectal cancer and potential vulnerabilities that might be targeted for cancer therapy.
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Affiliation(s)
- Yaqi Zhang
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Qiangjun Chen
- Department of Breast and Thyroid Surgery, Yi Du Central Hospital of Weifang, Shangdong Province No. 5168 Jiangjunshan Road Weifang 262500 China
| | - Lei Wang
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Haoyuan Geng
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Zihan Zhu
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Cancan Lv
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Yisheng Zhao
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Xiao Wang
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Chenglong Sun
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Panpan Chen
- Shandong Engineering Research Center for Innovation and Application of General Technology for Separation of Natural Products, Shandong Analysis and Test Center, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
- Key Laboratory for Natural Active Pharmaceutical Constituents Research in Universities of Shandong Province, School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences) Jinan 250014 China
| | - Chao Zhang
- Department of Pediatrics, Qilu Hospital of Shandong University Jinan 250012 China
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Jee H. Key Risk Factors, Sex Differences, and the Influence of High-Intensity Exercise on Colorectal Carcinogenesis: A 10-Year Cohort Study Based on 1,120,377 Individuals from the NHISS Data. Curr Oncol 2024; 31:7494-7510. [PMID: 39727676 DOI: 10.3390/curroncol31120553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Revised: 11/14/2024] [Accepted: 11/23/2024] [Indexed: 12/28/2024] Open
Abstract
Colorectal cancer (CRC) is the third most common cancer globally. Therefore, this study aims to examine data from the National Health Insurance Sharing Service (NHISS) to investigate factors influencing colon cancer incidence, focusing on key variables and optimal cutoff points. The patient cohort from the NHISS database included 1,120,377 individuals aged 1-85 years. CRC data were retrieved using diagnostic codes from the Korean Standard Classification of Diseases and Causes of Death. Analyses included logistic regression and receiver operating characteristic curve assessments. In this retrospective cohort study, 1,120,377 patients were analyzed for over 10 years, including 2802 with CRC via propensity score matching (PSM). Key risk factors were blood pressure, fasting blood sugar, liver somatic index, alcohol consumption, smoking duration, and hemoglobin levels. Patients with CRC showed sex differences in gamma-glutamyl transpeptidase (GGT). High-intensity exercise (3 days/week) reduced CRC risk by 26% (p < 0.05). Optimal threshold points for GGT and Charlson Comorbidity Index (CCI) were 23.50 U/L (AUC, 0.52) and 1.50 (AUC, 0.58), respectively. CCI scores were higher in patients with cancer, especially men with peptic ulcers and both sexes with metastatic cancer (p < 0.01). Our findings reveal new risk factors and interventions, including tailored exercise programs for CRC management, highlighting the importance of enhanced preventive strategies and personalized care.
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Affiliation(s)
- Hyunseok Jee
- School of Kinesiology, Yeungnam University, 280, Daehak-ro, Gyeongsan 38541, Gyeongbuk, Republic of Korea
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Eze-Odurukwe A, Rehman A, Ayinla L, Anika NN, Shahid R, Ugwuoru AL, Mansoor M, Kamran M. Metabolite Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review. Cureus 2024; 16:e74528. [PMID: 39726485 PMCID: PMC11671176 DOI: 10.7759/cureus.74528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/26/2024] [Indexed: 12/28/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with a poor prognosis. This poor prognosis is largely attributed to a late-stage diagnosis. Recent advancements in metabolomics have emerged as a promising avenue for biomarker discovery in PDAC. This systematic review evaluates the potential of metabolite biomarkers for early detection of PDAC. Four studies meeting the inclusion criteria were analyzed, encompassing experimental, case-control, and prospective cohort designs. Key findings include the identification of distinct metabolic subtypes in PDAC with varying sensitivities to metabolic inhibitors. A biomarker signature comprising nine metabolites plus CA19-9 showed high accuracy in distinguishing PDAC from chronic pancreatitis, outperforming CA19-9 alone. Another study identified a five-metabolite signature demonstrating high diagnostic accuracy for pancreatic cancer, differentiating it from type 2 diabetes mellitus. A two-metabolite model (isoleucine and adrenic acid) showed superior performance in detecting stage-I PDAC compared to CA19-9. These studies consistently demonstrate altered metabolic pathways in PDAC patients compared to healthy controls and those with benign pancreatic conditions. Integrating metabolomic data with other molecular profiling approaches has become a powerful strategy for improving diagnostic accuracy. However, challenges remain, including the influence of confounding factors, the need for large-scale validation studies, and the standardization of metabolomic methods. The potential of artificial intelligence in interpreting complex metabolomic data offers promising avenues for future research. This review highlights the significant potential of metabolite biomarkers in early PDAC detection while emphasizing the need for further validation and refinement of these approaches.
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Affiliation(s)
| | | | - Lois Ayinla
- General Medicine, All Saints University School of Medicine, Roseau, DMA
| | - Nabila N Anika
- Surgery, Baylor College of Medicine, Houston, USA
- Medicine and Surgery, Holy Family Red Crescent Medical College and Hospital, Dhaka, BGD
| | - Ramsha Shahid
- Physiology, Akhtar Saeed Medical and Dental College, Islamabad, PAK
| | | | - Muzafar Mansoor
- Internal Medicine, Allama Iqbal Medical College, Lahore, PAK
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Deng W, Ye C, Wang W, Huang R, Guo C, Pan Y, Sun C. LC-MS analysis of chiral amino acids in human urine reveals D-amino acids as potential biomarkers for colorectal cancer. J Chromatogr B Analyt Technol Biomed Life Sci 2024; 1245:124270. [PMID: 39121519 DOI: 10.1016/j.jchromb.2024.124270] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Revised: 07/27/2024] [Accepted: 08/04/2024] [Indexed: 08/12/2024]
Abstract
Colorectal cancer (CRC) is a common malignant tumor in the gastrointestinal tract. Changes in amino acid metabolites have been implicated in tumorigenesis and disease progression. Biomarkers on the basis of chiral amino acids, especially D-amino acids, have not been established for early diagnosis of CRC. Quantification of chiral amino acids, especially very low concentrations of endogenous D-amino acids, is technically challenging. We report here the quantification of L- and D-amino acids in urine samples collected from 115 CRC patients and 155 healthy volunteers, using an improved method. The method of chiral labeling, liquid chromatography, and tandem mass spectrometry enabled separation and detection of 28 amino acids (14 L-amino acids, 13 D-amino acids and Gly). Orthogonal partial least squares discriminant analysis identified 14 targeted variables among these chiral amino acids that distinguished the CRC from the healthy controls. Binary logistic regression analysis revealed that D-α-aminobutyric acid (D-AABA), L-alanine (L-Ala), D-alanine (D-Ala), D-glutamine (D-Gln) and D-serine (D-Ser) could be potential biomarkers for CRC. A receiver operating characteristic curve analysis of combined multi-variables contributed to an area under the curve (AUC) of 0.995 with 98.3 % sensitivity and 96.8 % specificity. A model constructed with D-AABA, D-Ala, D-Gln, and D-Ser achieved an AUC of 0.988, indicating important contributions of D-amino acids to the association with CRC. Further analysis also demonstrated that the metabolic aberration was associated with age and the development of CRC, D-methionine (D-Met) was decreased in CRC patients with age over 50, and D/L-Gln in patients at stage IV was higher than patients at stage I. This study provides the signature of D-amino acids in urine samples and offers a promising strategy for developing non-invasive diagnosis of CRC.
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Affiliation(s)
- Wenchan Deng
- State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Chundan Ye
- State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Wei Wang
- The Second Affiliated Hospital, Zhejiang University School of Medicine, Zijingang Campus of Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Rongrong Huang
- State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Cheng Guo
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
| | - Yuanjiang Pan
- Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310027, China.
| | - Cuirong Sun
- State Key Laboratory of Advanced Drug Delivery and Release Systems, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China.
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Sun J, Zhao J, Zhou S, Li X, Li T, Wang L, Yuan S, Chen D, Law PJ, Larsson SC, Farrington SM, Houlston RS, Dunlop MG, Theodoratou E, Li X. Systematic investigation of genetically determined plasma and urinary metabolites to discover potential interventional targets for colorectal cancer. J Natl Cancer Inst 2024; 116:1303-1312. [PMID: 38648753 PMCID: PMC11308169 DOI: 10.1093/jnci/djae089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2024] [Revised: 03/27/2024] [Accepted: 04/13/2024] [Indexed: 04/25/2024] Open
Abstract
BACKGROUND We aimed to identify plasma and urinary metabolites related to colorectal cancer (CRC) risk and elucidate their mediator role in the associations between modifiable risk factors and CRC. METHODS Metabolite quantitative trait loci were derived from 2 published metabolomics genome-wide association studies, and summary-level data were extracted for 651 plasma metabolites and 208 urinary metabolites. Genetic associations with CRC were obtained from a large-scale genome-wide association study meta-analysis (100 204 cases, 154 587 controls) and the FinnGen cohort (4957 cases, 304 197 controls). Mendelian randomization and colocalization analyses were performed to evaluate the causal roles of metabolites in CRC. Druggability evaluation was employed to prioritize potential therapeutic targets. Multivariable Mendelian randomization and mediation estimation were conducted to elucidate the mediating effects of metabolites on the associations between modifiable risk factors and CRC. RESULTS The study identified 30 plasma metabolites and 4 urinary metabolites for CRC. Plasma sphingomyelin and urinary lactose, which were positively associated with CRC risk, could be modulated by drug interventions (ie, olipudase alfa, tilactase). Thirteen modifiable risk factors were associated with 9 metabolites, and 8 of these modifiable risk factors were associated with CRC risk. These 9 metabolites mediated the effect of modifiable risk factors (Actinobacteria, body mass index, waist to hip ratio, fasting insulin, smoking initiation) on CRC. CONCLUSION This study identified key metabolite biomarkers associated with CRC and elucidated their mediator roles in the associations between modifiable risk factors and CRC. These findings provide new insights into the etiology and potential therapeutic targets for CRC and the etiological pathways of modifiable environmental factors with CRC.
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Affiliation(s)
- Jing Sun
- Department of Big Data in Health Science School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Jianhui Zhao
- Department of Big Data in Health Science School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Siyun Zhou
- Department of Big Data in Health Science School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Xinxuan Li
- Department of Big Data in Health Science School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Tengfei Li
- Department of Big Data in Health Science School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Lijuan Wang
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK
| | - Shuai Yuan
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Dong Chen
- Department of Colorectal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Philip J Law
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
| | - Susanna C Larsson
- Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
- Unit of Medical Epidemiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Susan M Farrington
- Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - Richard S Houlston
- Division of Genetics and Epidemiology, The Institute of Cancer Research, London, UK
| | - Malcolm G Dunlop
- Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
- Colon Cancer Genetics Group, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - Evropi Theodoratou
- Centre for Global Health, Usher Institute, University of Edinburgh, Edinburgh, UK
- Colon Cancer Genetics Group, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - Xue Li
- Department of Big Data in Health Science School of Public Health, and Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
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González A, Odriozola I, Fullaondo A, Odriozola A. Microbiota and detrimental protein derived metabolites in colorectal cancer. ADVANCES IN GENETICS 2024; 112:255-308. [PMID: 39396838 DOI: 10.1016/bs.adgen.2024.06.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/15/2024]
Abstract
Colorectal cancer (CRC) is the third leading cancer in incidence and the second leading cancer in mortality worldwide. There is growing scientific evidence to support the crucial role of the gut microbiota in the development of CRC. The gut microbiota is the complex community of microorganisms that inhabit the host gut in a symbiotic relationship. Diet plays a crucial role in modulating the risk of CRC, with a high intake of red and processed meat being a risk factor for the development of CRC. The production of metabolites derived from protein fermentation by the gut microbiota is considered a crucial element in the interaction between red and processed meat consumption and the development of CRC. This paper examines several metabolites derived from the bacterial fermentation of proteins associated with an increased risk of CRC. These metabolites include ammonia, polyamines, trimethylamine N-oxide (TMAO), N-nitroso compounds (NOC), hydrogen sulphide (H2S), phenolic compounds (p-cresol) and indole compounds (indolimines). These compounds are depicted and reviewed for their association with CRC risk, possible mechanisms promoting carcinogenesis and their relationship with the gut microbiota. Additionally, this paper analyses the evidence related to the role of red and processed meat intake and CRC risk and the factors and pathways involved in bacterial proteolytic fermentation in the large intestine.
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Affiliation(s)
- Adriana González
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain.
| | - Iñaki Odriozola
- Health Department of Basque Government, Donostia-San Sebastián, Spain
| | - Asier Fullaondo
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
| | - Adrian Odriozola
- Hologenomics Research Group, Department of Genetics, Physical Anthropology, and Animal Physiology, University of the Basque Country, Spain
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Xu C, Xu M, Hu Y, Liu J, Cheng P, Zeng Z, Pu K. Ingestible Artificial Urinary Biomarker Probes for Urine Test of Gastrointestinal Cancer. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2314084. [PMID: 38446383 DOI: 10.1002/adma.202314084] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 03/05/2024] [Indexed: 03/07/2024]
Abstract
Although colorectal cancer diagnosed at an early stage shows high curability, methods simultaneously possessing point-of-care testing ability and high sensitivity are limited. Here, an orally deliverable biomarker-activatable probe (termed as HATS) for early detection of orthotopic tumors via remote urinalysis is presented. To enable its oral delivery to the colon, HATS is designed to have remarkable resistance to acidity and digestive enzymes in the stomach and small intestine and negligible intestinal absorption. Upon reaction with a cancer biomarker in the colon segment, HATS releases a small fragment of tetrazine that can transverse the intestinal barrier, enter blood circulation, and ultimately undergo renal clearance to urine. Subsequently, the urinary tetrazine fragment is detected by bioorthogonal reaction with trans-cyclooctene-caged resorufin (TCO-Reso) to afford a rapid and specific fluorescence enhancement of TCO-Reso. Such signal readout is correlated with the urinary tetrazine concentration and thus measures the level of cancer biomarkers in the colon. HATS-based optical urinalysis detects orthotopic colon tumors two weeks earlier than clinical serological tests and can be developed to a point-of-care paper test. Thereby, HATS-based urinalysis provides a non-invasive and sensitive approach to cancer screening at low-resource settings.
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Affiliation(s)
- Cheng Xu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore
| | - Mengke Xu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore
| | - Yuxuan Hu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore
| | - Jing Liu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore
| | - Penghui Cheng
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore
| | - Ziling Zeng
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore
| | - Kanyi Pu
- School of Chemistry, Chemical Engineering and Biotechnology, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, 59 Nanyang Drive, Singapore, 636921, Singapore
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Huang YW, Chen HZ, Niu B, Wu W, Gao H, Yu J, Wang LS. Black raspberry-mediated metabolic changes in patients with familial adenomatous polyposis associated with rectal polyp regression. FOOD FRONTIERS 2024; 5:259-266. [PMID: 38779578 PMCID: PMC11107796 DOI: 10.1002/fft2.323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2024] Open
Abstract
Familial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, while the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry-based non-targeted metabolomics, we analyzed pre- and post-BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post-BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.
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Affiliation(s)
- Yi-Wen Huang
- Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Hui-zhi Chen
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Post-Harvest Fruit Processing, Key Laboratory of Post-Harvest Vegetable Preservation and Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fruit and Vegetable Preservation and Processing Technology of Zhejiang Province, Key Laboratory of Light Industry Fruit and Vegetable Preservation and Processing, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Ben Niu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Post-Harvest Fruit Processing, Key Laboratory of Post-Harvest Vegetable Preservation and Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fruit and Vegetable Preservation and Processing Technology of Zhejiang Province, Key Laboratory of Light Industry Fruit and Vegetable Preservation and Processing, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Weijie Wu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Post-Harvest Fruit Processing, Key Laboratory of Post-Harvest Vegetable Preservation and Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fruit and Vegetable Preservation and Processing Technology of Zhejiang Province, Key Laboratory of Light Industry Fruit and Vegetable Preservation and Processing, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Haiyan Gao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Post-Harvest Fruit Processing, Key Laboratory of Post-Harvest Vegetable Preservation and Processing, Ministry of Agriculture and Rural Affairs, Key Laboratory of Fruit and Vegetable Preservation and Processing Technology of Zhejiang Province, Key Laboratory of Light Industry Fruit and Vegetable Preservation and Processing, Institute of Food Science, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, China
| | - Jianhua Yu
- Department of Hematology and Hematopoietic Cell Transplantation, Comprehensive Cancer Center, City of Hope National Medical Center, Duarte, CA, USA
| | - Li-Shu Wang
- Department of Hematology and Hematopoietic Cell Transplantation, Comprehensive Cancer Center, City of Hope National Medical Center, Duarte, CA, USA
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10
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Zhou M, Wang Q, Lu X, Zhang P, Yang R, Chen Y, Xia J, Chen D. Exhaled breath and urinary volatile organic compounds (VOCs) for cancer diagnoses, and microbial-related VOC metabolic pathway analysis: a systematic review and meta-analysis. Int J Surg 2024; 110:1755-1769. [PMID: 38484261 PMCID: PMC10942174 DOI: 10.1097/js9.0000000000000999] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Accepted: 12/04/2023] [Indexed: 03/17/2024]
Abstract
BACKGROUND The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors. MATERIALS AND METHODS An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and specificity of the VOCs for cancer detection. Fagan's nomogram was designed to leverage the findings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota. RESULTS The pooled sensitivity, specificity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0.89, 0.88, and 0.95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the 'ruling in' approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the 'ruling out' approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identified in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in the aforementioned tumor types. CONCLUSIONS The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These findings hold significant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets.
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Affiliation(s)
- Min Zhou
- Department of Breast Surgery, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi Maternity and Child Health Care Hospital
| | - Qinghua Wang
- Research Institute for Reproductive Health and Genetic Diseases, Women’s Hospital of Jiangnan University
| | - Xinyi Lu
- Department of Breast Surgery, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi Maternity and Child Health Care Hospital
| | - Ping Zhang
- Department of Breast Surgery, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi Maternity and Child Health Care Hospital
| | - Rui Yang
- Research Institute for Reproductive Health and Genetic Diseases, Women’s Hospital of Jiangnan University
| | - Yu Chen
- Research Institute for Reproductive Health and Genetic Diseases, Women’s Hospital of Jiangnan University
| | - Jiazeng Xia
- Department of General Surgery and Translational Medicine Center, The Affiliated Wuxi No. 2 People’s Hospital of Nanjing Medical University, Jiangnan University Medical Center, Wuxi, People’s Republic of China
| | - Daozhen Chen
- Department of Breast Surgery, The Affiliated Wuxi Maternity and Child Health Care Hospital of Nanjing Medical University, Wuxi Maternity and Child Health Care Hospital
- Research Institute for Reproductive Health and Genetic Diseases, Women’s Hospital of Jiangnan University
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11
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Bhattacharyya D, LeVatte MA, Wishart DS. A fast and accurate colorimetric assay for quantifying hippuric acid in human urine. Anal Biochem 2023; 680:115303. [PMID: 37689001 DOI: 10.1016/j.ab.2023.115303] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2023] [Revised: 08/18/2023] [Accepted: 08/30/2023] [Indexed: 09/11/2023]
Abstract
Hippuric acid is an abundant metabolite in human urine. Urinary hippuric acid levels change with toxic exposure to aromatic compounds, consumption of fruits and vegetables, cancers, chronic kidney disease, schizophrenia and Crohn's disease. While urinary hippuric acid can be detected and quantified via mass spectrometry or nuclear magnetic resonance spectroscopy, a colorimetric assay would be preferable for a low-cost, point-of care clinical assay. Two colorimetric methods, that use p-dimethylaminobenzaldehyde (DMAB) or benzenesulfonyl chloride (PhSO2Cl), respectively, have been previously developed to detect hippuric acid but these assays have many limitations. We replaced PhSO2Cl with p-toluenesulfonyl chloride (p-TsCl), to create a simpler, faster and more accurate method that works with human urine. This modified colorimetric assay detects from 60 μM to 1000 μM hippuric acid in urine in 2 min. We also corrected for the effects of interfering compounds present in urine such that the assay works across many urine backgrounds. We validated this improved assay on multiple hippurate-spiked urine samples, observing an excellent correlation (R2 > 0.94) between observed and known hippurate concentrations. These data suggest that this colorimetric assay is accurate and should greatly facilitate the measurement of hippuric acid in urine to detect a variety of human conditions.
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Affiliation(s)
| | - Marcia A LeVatte
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E8, Canada
| | - David S Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, AB, T6G 2E8, Canada; Department of Computing Science, University of Alberta, Edmonton, AB, T6G 2E9, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, T6G 2B7, Canada; Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, T6G 2H7, Canada.
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12
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Singh P, Yadav R, Verma M, Chhabra R. Analysis of the Inhibitory Effect of hsa-miR-145-5p and hsa-miR-203a-5p on Imatinib-Resistant K562 Cells by GC/MS Metabolomics Method. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2023; 34:2117-2126. [PMID: 37706267 DOI: 10.1021/jasms.3c00103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/15/2023]
Abstract
Imatinib (IM) resistance is considered to be a significant challenge in the management of chronic myeloid leukemia (CML). Previous studies have reported that hsa-miR-145-5p and hsa-miR-203a-5p can overcome IM resistance and hsa-miR-203a-5p can alter glutathione metabolism in IM-resistant cells. The purpose of this study was to examine whether hsa-miR-145-5p or hsa-miR-203a-5p counters IM resistance by targeting the overall metabolic profile of IM-resistant K562 cells. The metablic profiling of cell lysates obtained from IM-sensitive, IM-resistant, and miR-transfected IM-resistant K562 cells was carried out using the GC-MS technique. Overall, 75 major metabolites were detected, of which 32 were present in all samples. The pathway analysis of MetaboAnalyst 5.0 revealed that the majorly enriched pathways included glucose metabolism, fatty acid biosynthesis, lipogenesis, and nucleotide metabolism. Eleven of identified metabolites, l-glutamine, l-glutamic acid, l-lactic acid, phosphoric acid, 9,12-octadecadienoic acid, 9-octadecenoic acid, myristic acid, palmitic acid, cholesterol, and β-alanine, appeared in enriched pathways. IM-resistant cells had comparatively higher concentrations of all of these metabolites. Notably, the introduction of hsa-miR-145-5p or hsa-miR-203a-5p into resistant cells resulted in a decrease in levels of these metabolites. The efficacy of miR-203a-5p was particularly remarkable in comparison with miR-145-5p, as evidenced by partial least-squares-discriminant analysis (PLS-DA), which showed a high level of similarity in metabolic profile between IM-sensitive K562 cells and IM-resistant cells transfected with hsa-miR-203a-5p. The results indicate that GC-MS-based metabolic profiling has the potential to distinguish between drug-resistant and -sensitive cells. This approach can also be used to routinely monitor therapeutic response in drug-resistant patients, thus, enabling personalized therapy.
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Affiliation(s)
- Priyanka Singh
- Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda 151401, India
| | - Radheshyam Yadav
- Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda 151401, India
| | - Malkhey Verma
- School of Biotechnology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Ravindresh Chhabra
- Department of Biochemistry, School of Basic Sciences, Central University of Punjab, Ghudda, Bathinda 151401, India
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13
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Dai L, Yuan B, Zhang B, Chen W, Yuan X, Liu X, Gao Y, Zhang Y, Zhang Q, Zhao X. Gas/Liquid Chromatography-Mass Spectrometry Analysis of Key Functional Substances Regulating Poll Gland Secretion in Male Camels during Seasonal Estrus. Animals (Basel) 2023; 13:2024. [PMID: 37370534 DOI: 10.3390/ani13122024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2023] [Revised: 06/14/2023] [Accepted: 06/16/2023] [Indexed: 06/29/2023] Open
Abstract
Increased poll gland secretion is a major characteristic and indicator of estrus in male Bactrian camels; however, research on these poll glands and their secretion is extremely rare. In this study, we determine the chemical composition of poll gland secretions and identify the key functional substances that regulate seasonal estrus in male camels. A GC/LC-MS dual platform was used to analyze ventral hair (control) and neck mane samples containing poll gland secretions from male Bactrian camels during estrus. Multidimensional and single-dimensional analyses were used to screen differentially expressed metabolites (DEMs) between groups. Functional prediction of enriched metabolites was performed using a Human Metabolome Database comparison and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which were then compared with a behavioral analysis of male Bactrian camels in estrus. A total of 1172 DEMs and 34 differential metabolic pathways were identified. One metabolite group was found to relate to steroid synthesis and metabolism, and another metabolite group was associated with neural metabolism. Therefore, we speculate that steroids and neurochemicals jointly regulate estrous behavior in male Bactrian camels, thus providing theoretical insights into the development and function of poll glands in Bactrian camels.
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Affiliation(s)
- Lijun Dai
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Bao Yuan
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Bohao Zhang
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Wenli Chen
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Xixue Yuan
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Xinhong Liu
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Yuan Gao
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Yong Zhang
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
| | - Quanwei Zhang
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
| | - Xingxu Zhao
- College of Life Science and Biotechnology, Gansu Agricultural University, Lanzhou 730070, China
- Gansu Key Laboratory of Animal Generational Physiology and Reproductive Regulation, Lanzhou 730070, China
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou 730070, China
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14
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Clavenna MG, La Vecchia M, Sculco M, Joseph S, Barberis E, Amede E, Mellai M, Brossa S, Borgonovi G, Occhipinti P, Boldorini R, Robotti E, Azzimonti B, Bona E, Pasolli E, Ferrante D, Manfredi M, Aspesi A, Dianzani I. Distinct Signatures of Tumor-Associated Microbiota and Metabolome in Low-Grade vs. High-Grade Dysplastic Colon Polyps: Inference of Their Role in Tumor Initiation and Progression. Cancers (Basel) 2023; 15:3065. [PMID: 37370676 DOI: 10.3390/cancers15123065] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2023] [Revised: 05/31/2023] [Accepted: 06/01/2023] [Indexed: 06/29/2023] Open
Abstract
According to the driver-passenger model for colorectal cancer (CRC), the tumor-associated microbiota is a dynamic ecosystem of bacterial species where bacteria with carcinogenic features linked to CRC initiation are defined as "drivers", while opportunistic bacteria colonizing more advanced tumor stages are known as "passengers". We reasoned that also gut microbiota-associated metabolites may be differentially enriched according to tumor stage, and be potential determinants of CRC development. Thus, we characterized the mucosa- and lumen-associated microbiota (MAM and LAM, respectively) and mucosa-associated metabolites in low- vs. high-grade dysplastic colon polyps from 78 patients. We show that MAM, obtained with a new biopsy-preserving approach, and LAM differ in composition and α/β-diversity. By stratifying patients for polyp histology, we found that bacteria proposed as passengers by previous studies colonized high-grade dysplastic adenomas, whereas driver taxa were enriched in low-grade polyps. Furthermore, we report altered "mucosa-associated metabolite" levels in low- vs. high-grade groups. Integrated microbiota-metabolome analysis suggests the involvement of the gut microbiota in the production and consumption of these metabolites. Altogether, our findings support the involvement of bacterial species and associated metabolites in CRC mucosal homeostasis in a tumor-stage-specific manner. These distinct signatures may be used to distinguish low-grade from high-grade dysplastic polyps.
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Affiliation(s)
| | - Marta La Vecchia
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Marika Sculco
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Soni Joseph
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Elettra Barberis
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, 28100 Novara, Italy
| | - Elia Amede
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, 28100 Novara, Italy
| | - Marta Mellai
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, 28100 Novara, Italy
| | - Silvia Brossa
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Giulia Borgonovi
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Pietro Occhipinti
- Department of Gastroenterology, "Maggiore della Carità" Hospital, 28100 Novara, Italy
| | - Renzo Boldorini
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Elisa Robotti
- Department of Sciences and Technological Innovation, Università del Piemonte Orientale, 15121 Alessandria, Italy
| | - Barbara Azzimonti
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, 28100 Novara, Italy
| | - Elisa Bona
- Department for Sustainable Development and Ecological Transition, Università del Piemonte Orientale, 13100 Vercelli, Italy
| | - Edoardo Pasolli
- Department of Agricultural Sciences, University of Naples Federico II, 80055 Portici, Italy
- Task Force on Microbiome Studies, University of Naples Federico II, 80055 Portici, Italy
| | - Daniela Ferrante
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Marcello Manfredi
- Department of Translational Medicine, Università del Piemonte Orientale, 28100 Novara, Italy
- Center for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, 28100 Novara, Italy
| | - Anna Aspesi
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
| | - Irma Dianzani
- Department of Health Sciences, Università del Piemonte Orientale, 28100 Novara, Italy
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15
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Jordaens S, Zwaenepoel K, Tjalma W, Deben C, Beyers K, Vankerckhoven V, Pauwels P, Vorsters A. Urine biomarkers in cancer detection: A systematic review of preanalytical parameters and applied methods. Int J Cancer 2023; 152:2186-2205. [PMID: 36647333 DOI: 10.1002/ijc.34434] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 11/25/2022] [Accepted: 12/29/2022] [Indexed: 01/18/2023]
Abstract
The aim of this review was to explore the status of urine sampling as a liquid biopsy for noninvasive cancer research by reviewing used preanalytical parameters and protocols. We searched two main health sciences databases, PubMed and Web of Science. From all eligible publications (2010-2022), information was extracted regarding: (a) study population characteristics, (b) cancer type, (c) urine preanalytics, (d) analyte class, (e) isolation method, (f) detection method, (g) comparator used, (h) biomarker type, (i) conclusion and (j) sensitivity and specificity. The search query identified 7835 records, of which 924 unique publications remained after screening the title, abstract and full text. Our analysis demonstrated that many publications did not report information about the preanalytical parameters of their urine samples, even though several other studies have shown the importance of standardization of sample handling. Interestingly, it was noted that urine is used for many cancer types and not just cancers originating from the urogenital tract. Many different types of relevant analytes have been shown to be found in urine. Additionally, future considerations and recommendations are discussed: (a) the heterogeneous nature of urine, (b) the need for standardized practice protocols and (c) the road toward the clinic. Urine is an emerging liquid biopsy with broad applicability in different analytes and several cancer types. However, standard practice protocols for sample handling and processing would help to elaborate the clinical utility of urine in cancer research, detection and disease monitoring.
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Affiliation(s)
- Stephanie Jordaens
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Novosanis NV, Wijnegem, Belgium
| | - Karen Zwaenepoel
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Laboratory of Pathological Anatomy, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Wiebren Tjalma
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Multidisciplinary Breast Clinic, Gynecological Oncology Unit, Department of Obstetrics and Gynecology, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Christophe Deben
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium
| | | | - Vanessa Vankerckhoven
- Novosanis NV, Wijnegem, Belgium.,Center for Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
| | - Patrick Pauwels
- Center for Oncological Research (CORE), Integrated Personalized & Precision Oncology Network (IPPON), University of Antwerp, Wilrijk, Belgium.,Laboratory of Pathological Anatomy, Antwerp University Hospital (UZA), Edegem, Belgium
| | - Alex Vorsters
- Center for Evaluation of Vaccination (CEV), Vaccine & Infectious Disease Institute (VAXINFECTIO), Faculty of Medicine and Health Sciences, University of Antwerp, Wilrijk, Belgium
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16
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Song G, Wang L, Tang J, Li H, Pang S, Li Y, Liu L, Hu J. Circulating metabolites as potential biomarkers for the early detection and prognosis surveillance of gastrointestinal cancers. Metabolomics 2023; 19:36. [PMID: 37014438 PMCID: PMC10073066 DOI: 10.1007/s11306-023-02002-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 03/22/2023] [Indexed: 04/05/2023]
Abstract
BACKGROUND AND AIMS Two of the most lethal gastrointestinal (GI) cancers, gastric cancer (GC) and colon cancer (CC), are ranked in the top five cancers that cause deaths worldwide. Most GI cancer deaths can be reduced by earlier detection and more appropriate medical treatment. Unlike the current "gold standard" techniques, non-invasive and highly sensitive screening tests are required for GI cancer diagnosis. Here, we explored the potential of metabolomics for GI cancer detection and the classification of tissue-of-origin, and even the prognosis management. METHODS Plasma samples from 37 gastric cancer (GC), 17 colon cancer (CC), and 27 non-cancer (NC) patients were prepared for metabolomics and lipidomics analysis by three MS-based platforms. Univariate, multivariate, and clustering analyses were used for selecting significant metabolic features. ROC curve analysis was based on a series of different binary classifications as well as the true-positive rate (sensitivity) and the false-positive rate (1-specificity). RESULTS GI cancers exhibited obvious metabolic perturbation compared with benign diseases. The differentiated metabolites of gastric cancer (GC) and colon cancer (CC) were targeted to same pathways but with different degrees of cellular metabolism reprogramming. The cancer-specific metabolites distinguished the malignant and benign, and classified the cancer types. We also applied this test to before- and after-surgery samples, wherein surgical resection significantly altered the blood-metabolic patterns. There were 15 metabolites significantly altered in GC and CC patients who underwent surgical treatment, and partly returned to normal conditions. CONCLUSION Blood-based metabolomics analysis is an efficient strategy for GI cancer screening, especially for malignant and benign diagnoses. The cancer-specific metabolic patterns process the potential for classifying tissue-of-origin in multi-cancer screening. Besides, the circulating metabolites for prognosis management of GI cancer is a promising area of research.
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Affiliation(s)
- Guodong Song
- The Second Hospital of Tianjin Medical University, No 23. Pingjiang Road, Hexi District, 300211, Tianjin, China
| | - Li Wang
- The Second Hospital of Tianjin Medical University, No 23. Pingjiang Road, Hexi District, 300211, Tianjin, China
| | - Junlong Tang
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Haohui Li
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Shuyu Pang
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Yan Li
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China
| | - Li Liu
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China.
| | - Junyuan Hu
- Metanotitia Inc, No 59. Gaoxin South 9Th Road, Yuehai Street, Nanshan District, Shenzhen, 518056, Guangdong, China.
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17
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van Liere ELSA, van Dijk LJ, Bosch S, Vermeulen L, Heymans MW, Burchell GL, de Meij TGJ, Ramsoekh D, de Boer NKH. Urinary volatile organic compounds for colorectal cancer screening, a systematic review and meta-analysis. Eur J Cancer 2023; 186:69-82. [PMID: 37030079 DOI: 10.1016/j.ejca.2023.03.002] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 03/02/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023]
Abstract
BACKGROUND The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds (VOCs) may be a useful alternative. We aimed to determine the diagnostic potential of urinary VOCs for CRC/adenomas. By relating VOCs to known pathways, we aimed to gain insight into the pathophysiology of colorectal neoplasia. METHODS A systematic search was performed in PubMed, EMBASE and Web of Science. Original studies on urinary VOCs for CRC/adenoma detection with a control group were included. QUADAS-2 tool was used for quality assessment. Meta-analysis was performed by adopting a bivariate model for sensitivity/specificity. Fagan's nomogram estimated the performance of combined FIT-VOC. Neoplasm-associated VOCs were linked to pathways using the KEGG database. RESULTS Sixteen studies-involving 837 CRC patients and 1618 controls-were included; 11 performed chemical identification and 7 chemical fingerprinting. In all studies, urinary VOCs discriminated CRC from controls. Pooled sensitivity and specificity for CRC based on chemical fingerprinting were 84% (95% CI 73-91%) and 70% (95% CI 63-77%), respectively. The most distinctive individual VOC was butanal (AUC 0.98). The estimated probability of having CRC following negative FIT was 0.38%, whereas 0.09% following negative FIT-VOC. Combined FIT-VOC would detect 33% more CRCs. In total 100 CRC-associated urinary VOCs were identified; particularly hydrocarbons, carboxylic acids, aldehydes/ketones and amino acids, and predominantly involved in TCA-cycle or alanine/aspartate/glutamine/glutamate/phenylalanine/tyrosine/tryptophan metabolism, which is supported by previous research on (colorectal)cancer biology. The potential of urinary VOCs to detect precancerous adenomas or gain insight into their pathophysiology appeared understudied. CONCLUSION Urinary VOCs hold potential for non-invasive CRC screening. Multicentre validation studies are needed, especially focusing on adenoma detection. Urinary VOCs elucidate underlying pathophysiologic processes.
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Affiliation(s)
- Elsa L S A van Liere
- Amsterdam University Medical Centres, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam, the Netherlands; Vrije Universiteit, School of Medicine, Amsterdam, the Netherlands.
| | - Laura J van Dijk
- Amsterdam University Medical Centres, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Vrije Universiteit, School of Medicine, Amsterdam, the Netherlands
| | - Sofie Bosch
- Amsterdam University Medical Centres, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam, the Netherlands
| | - Louis Vermeulen
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam, the Netherlands; Amsterdam UMC location University of Amsterdam, Laboratory for Experimental Oncology and Radiobiology, Centre for Experimental and Molecular Medicine, Amsterdam, the Netherlands; Cancer Centre Amsterdam, Amsterdam, the Netherlands; Oncode Institute, Amsterdam, the Netherlands
| | - Martijn W Heymans
- Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Epidemiology and Data Science, Amsterdam, the Netherlands
| | - George L Burchell
- Medical Library, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
| | - Tim G J de Meij
- Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam, the Netherlands; Amsterdam UMC location Vrije Universiteit Amsterdam, Department of Paediatric Gastroenterology, Amsterdam, the Netherlands
| | - Dewkoemar Ramsoekh
- Amsterdam University Medical Centres, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam, the Netherlands; Vrije Universiteit, School of Medicine, Amsterdam, the Netherlands
| | - Nanne K H de Boer
- Amsterdam University Medical Centres, Department of Gastroenterology and Hepatology, Amsterdam, the Netherlands; Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam, the Netherlands; Vrije Universiteit, School of Medicine, Amsterdam, the Netherlands
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18
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Jalandra R, Makharia GK, Sharma M, Kumar A. Inflammatory and deleterious role of gut microbiota-derived trimethylamine on colon cells. Front Immunol 2023; 13:1101429. [PMID: 36726978 PMCID: PMC9885123 DOI: 10.3389/fimmu.2022.1101429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Accepted: 12/28/2022] [Indexed: 01/18/2023] Open
Abstract
Trimethylamine (TMA) is produced by the intestinal microbiota as a by-product of metabolism of dietary precursors. TMA has been implicated in various chronic health conditions. However, the effect of TMA in the colon and the underlying mechanism was not clear. In this study, TMA exhibited toxic effects in vitro as well as in vivo. TMA-induced oxidative stress causes DNA damage, and compromised cell membrane integrity leading to the release of LDH outside the cells which ultimately leads to cell death. Besides, TMA also exhibited pronounced increase in cell cycle arrest at G2/M phase in both HCT116 and HT29 cell lines. TMA was found to be genotoxic and cytotoxic as the TMA concentration increased from 0.15 mM. A decreased ATP intracellular content was observed after 24 h, 48 h, and 72 h treatment in a time and dose-dependent manner. For in vivo research, TMA (100 mM, i.p. and intra-rectal) once a week for 12 weeks caused significant changes in cellular morphology of colon and rectum epithelium as assessed by H & E staining. TMA also significantly increased the infiltration of inflammatory cells in the colon and rectal epithelium indicating the severity of inflammation. In addition, TMA caused extensive mucosal damage and distortion in the epithelium, decrease in length of small intestine compared to control mice. In conclusion, these results highlight the detrimental effects of TMA in the colon and rectal epithelium.
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Affiliation(s)
- Rekha Jalandra
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi, India
- Department of Zoology, Maharshi Dayanand University, Rohtak, India
| | - Govind K. Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Minakshi Sharma
- Department of Zoology, Maharshi Dayanand University, Rohtak, India
| | - Anil Kumar
- Gene Regulation Laboratory, National Institute of Immunology, New Delhi, India
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Zhang P, Lan X, Fan B, Chen Y, Wei X, Li X, Fan N, Tang C, Lu L. A protocol for the integration of multi-omics bioinformatics: Mechanism of acupuncture as an adjunctive therapy for alcohol use disorder. Front Neurol 2023; 13:977487. [PMID: 36686540 PMCID: PMC9849375 DOI: 10.3389/fneur.2022.977487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 11/28/2022] [Indexed: 01/06/2023] Open
Abstract
Background Alcohol use disorder (AUD) has become a significant global factor in various diseases. As a non-pharmacological therapy, certain therapeutic potential has been found in acupuncture; however, in-depth mechanistic studies related to acupuncture for patients with AUD are still insufficient. Methods Based on a randomized control design and a multi-omics analysis plan, this protocol details the recruitment (42 AUD patients), group allocation (21 in acupuncture group vs. 21 in sham acupuncture group), intervention and follow-up (replacement drugs as a normal treatment, 2 weeks acupuncture duration, and 3 month follow-up), and data collection and analytical processes. For the clinical outcomes, in addition to the time required for alcohol withdrawal symptoms to subside as the primary outcome, changes in the alcohol withdrawal symptoms, alcohol craving, mood dysfunction, sleep disorder, fatigue, self-efficacy, gastrointestinal symptoms, the quality of life, and the relapse outcomes will be compared between the groups to confirm the acupuncture clinical effectiveness on alcohol withdraw. The gut microbiome and the fecal metabolomics will also be assessed to explore the association of the structure and the function of gut microflora and the mediation of acupuncture effect on AUD fully utilizing gut microflora multi-modal data and clinical information, via the combination of multi-omics methods, feature screening algorithms and appropriate models. Discussion The results of this study may help to strengthen clinical evidence of the mechanism of acupuncture intervention in patients with AUD, through understanding of the regulatory mechanism of acupuncture in the gut microbiome and its metabolism as well as AUD-related clinical manifestations. Trial registration Chinese Clinical Trial Registry ChiCTR2200058120. Registered on 24 Mar 2022.
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Affiliation(s)
- Peiming Zhang
- Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Xiaochang Lan
- Department of Substance Dependence, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong Province, China
| | - Baochao Fan
- Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Yiming Chen
- Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Xiaojing Wei
- Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Xiangli Li
- Department of Chinese Medicine, Guangzhou First People's Hospital, Guangzhou, Guangdong Province, China
| | - Ni Fan
- Department of Substance Dependence, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, Guangdong Province, China
| | - Chunzhi Tang
- Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
| | - Liming Lu
- Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong Province, China
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20
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Zhang L, Zheng J, Ismond KP, MacKay S, LeVatte M, Constable J, Alatise OI, Kingham TP, Wishart DS. Identification of urinary biomarkers of colorectal cancer: Towards the development of a colorectal screening test in limited resource settings. Cancer Biomark 2023; 36:17-30. [PMID: 35871322 PMCID: PMC10627333 DOI: 10.3233/cbm-220034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
BACKGROUND African colorectal cancer (CRC) rates are rising rapidly. A low-cost CRC screening approach is needed to identify CRC from non-CRC patients who should be sent for colonoscopy (a scarcity in Africa). OBJECTIVE To identify urinary metabolite biomarkers that, combined with easy-to-measure clinical variables, would identify patients that should be further screened for CRC by colonoscopy. Ideal metabolites would be water-soluble and easily translated into a sensitive, low-cost point-of-care (POC) test. METHODS Liquid-chromatography mass spectrometry (LC-MS/MS) was used to quantify 142 metabolites in spot urine samples from 514 Nigerian CRC patients and healthy controls. Metabolite concentration data and clinical characteristics were used to determine optimal sets of biomarkers for identifying CRC from non-CRC subjects. RESULTS Our statistical analysis identified N1, N12-diacetylspermine, hippurate, p-hydroxyhippurate, and glutamate as the best metabolites to discriminate CRC patients via POC screening. Logistic regression modeling using these metabolites plus clinical data achieved an area under the receiver-operator characteristic (AUCs) curves of 89.2% for the discovery set, and 89.7% for a separate validation set. CONCLUSIONS Effective urinary biomarkers for CRC screening do exist. These results could be transferred into a simple, POC urinary test for screening CRC patients in Africa.
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Affiliation(s)
- Lun Zhang
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Jiamin Zheng
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | | | - Scott MacKay
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Marcia LeVatte
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
| | - Jeremy Constable
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Olusegun Isaac Alatise
- Department of Surgery, Obafemi Awolowo University and Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - David S. Wishart
- Department of Biological Sciences, University of Alberta, Edmonton, AB, Canada
- Department of Computing Science, University of Alberta, Edmonton, AB, Canada
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21
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Systematic Review: Contribution of the Gut Microbiome to the Volatile Metabolic Fingerprint of Colorectal Neoplasia. Metabolites 2022; 13:metabo13010055. [PMID: 36676980 PMCID: PMC9865897 DOI: 10.3390/metabo13010055] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2022] [Revised: 12/16/2022] [Accepted: 12/22/2022] [Indexed: 12/31/2022] Open
Abstract
Colorectal cancer (CRC) has been associated with changes in volatile metabolic profiles in several human biological matrices. This enables its non-invasive detection, but the origin of these volatile organic compounds (VOCs) and their relation to the gut microbiome are not yet fully understood. This systematic review provides an overview of the current understanding of this topic. A systematic search using PubMed, Embase, Medline, Cochrane Library, and the Web of Science according to PRISMA guidelines resulted in seventy-one included studies. In addition, a systematic search was conducted that identified five systematic reviews from which CRC-associated gut microbiota data were extracted. The included studies analyzed VOCs in feces, urine, breath, blood, tissue, and saliva. Eight studies performed microbiota analysis in addition to VOC analysis. The most frequently reported dysregulations over all matrices included short-chain fatty acids, amino acids, proteolytic fermentation products, and products related to the tricarboxylic acid cycle and Warburg metabolism. Many of these dysregulations could be related to the shifts in CRC-associated microbiota, and thus the gut microbiota presumably contributes to the metabolic fingerprint of VOC in CRC. Future research involving VOCs analysis should include simultaneous gut microbiota analysis.
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22
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Khan H, Shah MR, Barek J, Malik MI. Cancer biomarkers and their biosensors: A comprehensive review. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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23
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Zeng J, Peng J, Jiang H, Deng P, Li K, Long D, Wang K. Establishment of an early diagnosis model of colon cancerous bowel obstruction based on 1H NMR. PLoS One 2022; 17:e0266730. [PMID: 35972924 PMCID: PMC9380946 DOI: 10.1371/journal.pone.0266730] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Accepted: 03/28/2022] [Indexed: 11/23/2022] Open
Abstract
Objective To prospectively establish an early diagnosis model of acute colon cancerous bowel obstruction by applying nuclear magnetic resonance hydrogen spectroscopy(1H NMR) technology based metabolomics methods, combined with machine learning. Methods In this study, serum samples of 71 patients with acute bowel obstruction requiring emergency surgery who were admitted to the Emergency Department of Sichuan Provincial People’s Hospital from December 2018 to November 2020 were collected within 2 hours after admission, and NMR spectroscopy data was taken after pretreatment. After postoperative pathological confirmation, they were divided into colon cancerous bowel obstruction (CBO) group and adhesive bowel obstruction (ABO) control group. Used MestReNova software to extract the two sets of spectra bins, and used the MetaboAnalyst5.0 website to perform partial least square discrimination (PLS-DA), combining the human metabolome database (HMDB) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find possible different Metabolites and related metabolic pathways. Results 22 patients were classified as CBO group and 30 were classified as ABO control group. Compared with ABO group, the level of Xanthurenic acid, 3-Hydroxyanthranilic acid, Gentisic acid, Salicyluric acid, Ferulic acid, Kynurenic acid, CDP, Mandelic acid, NADPH, FAD, Phenylpyruvate, Allyl isothiocyanate, and Vanillylmandelic acid increased in the CBO group; while the lecel of L-Tryptophan and Bilirubin decreased. There were significant differences between two groups in the tryptophan metabolism, tyrosine metabolism, glutathione metabolism, phenylalanine metabolism and synthesis pathways of phenylalanine, tyrosine and tryptophan (all P<0.05). Tryptophan metabolism pathway had the greatest impact (Impact = 0.19). The early diagnosis model of colon cancerous bowel was established based on the levels of six metabolites: Xanthurenic acid, 3-Hydroxyanthranilic acid, Gentisic acid, Salicylic acid, Ferulic acid and Kynurenic acid (R2 = 0.995, Q2 = 0.931, RMSE = 0.239, AUC = 0.962). Conclusion This study firstly used serum to determine the difference in metabolome between patients with colon cancerous bowel obstruction and those with adhesive bowel obstruction. The study found that the metabolic information carried by the serum was sufficient to discriminate the two groups of patients and provided the theoretical supporting for the future using of the more convenient sample for the differential diagnosis of patients with colon cancerous bowel obstruction. Quantitative experiments on a large number of samples were still needed in the future.
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Affiliation(s)
- Jie Zeng
- Department of Emergency Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, P.R. China
| | - Jin Peng
- Department of Histology Embryology and Neurobiology, Sichuan University West China School of Basic Medical Sciences and Forensic Medicine, Chengdu, Sichuan, P.R. China
- * E-mail:
| | - Hua Jiang
- Department of Emergency Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, P.R. China
| | - Pengchi Deng
- Analytical and Testing Center, Sichuan University, Chengdu, Sichuan, P.R. China
| | - Kexun Li
- Department of Emergency Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, P.R. China
| | - Daolin Long
- Department of Emergency Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, P.R. China
| | - Kai Wang
- Department of Emergency Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, Sichuan, P.R. China
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24
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Lu G, Zhou J, Yang T, Li J, Jiang X, Zhang W, Gu S, Wang J. Landscape of Metabolic Fingerprinting for Diagnosis and Risk Stratification of Sepsis. Front Immunol 2022; 13:883628. [PMID: 35663956 PMCID: PMC9159301 DOI: 10.3389/fimmu.2022.883628] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2022] [Accepted: 04/19/2022] [Indexed: 11/13/2022] Open
Abstract
Background Sepsis and septic shock, a subset of sepsis with higher risk stratification, are hallmarked by high mortality rates and necessitated early and accurate biomarkers. Methods Untargeted metabolomic analysis was performed to compare the metabolic features between the sepsis and control systemic inflammatory response syndrome (SIRS) groups in discovery cohort, and potential metabolic biomarkers were selected and quantified using multiple reaction monitoring based target metabolite detection method. Results Differentially expressed metabolites including 46 metabolites in positive electrospray ionization (ESI) ion mode, 22 metabolites in negative ESI ion mode, and 4 metabolites with dual mode between sepsis and SIRS were identified and revealed. Metabolites 5-Oxoproline, L-Kynurenine and Leukotriene D4 were selected based on least absolute shrinkage and selection operator regularization logistic regression and differential expressed between sepsis and septic shock group in the training and test cohorts. Respective risk scores for sepsis and septic shock based on a 3-metabolite fingerprint classifier were established to distinguish sepsis from SIRS, septic shock from sepsis. Significant relationship between developed sepsis risk scores, septic shock risk scores and Sequential (sepsis-related) Organ Failure Assessment (SOFA), procalcitonin (PCT) and lactic acid were observed. Conclusions Collectively, our findings demonstrated that the characteristics of plasma metabolites not only manifest phenotypic variation in sepsis onset and risk stratification of sepsis but also enable individualized treatment and improve current therapeutic strategies.
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Affiliation(s)
- Geng Lu
- Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jiawei Zhou
- Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Ting Yang
- Department of Pharmacy, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jin Li
- Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Xinrui Jiang
- Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Wenjun Zhang
- Departments of Laboratory Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Shuangshuang Gu
- Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Jun Wang
- Department of Emergency, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
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25
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Powles STR, Gallagher KI, Chong LWL, Alexander JL, Mullish BH, Hicks LC, McDonald JAK, Marchesi JR, Williams HRT, Orchard TR. Effects of bowel preparation on intestinal bacterial associated urine and faecal metabolites and the associated faecal microbiome. BMC Gastroenterol 2022; 22:240. [PMID: 35562657 PMCID: PMC9101932 DOI: 10.1186/s12876-022-02301-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2021] [Accepted: 04/20/2022] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND Urinary and faecal metabolic profiling have been extensively studied in gastrointestinal diseases as potential diagnostic markers, and to enhance our understanding of the intestinal microbiome in the pathogenesis these conditions. The impact of bowel cleansing on the microbiome has been investigated in several studies, but limited to just one study on the faecal metabolome. AIM To compare the effects of bowel cleansing on the composition of the faecal microbiome, and the urine and faecal metabolome. METHODS Urine and faecal samples were obtained from eleven patients undergoing colonoscopy at baseline, and then at day 3 and week 6 after colonoscopy. 16S rRNA gene sequencing was used to analyse changes in the microbiome, and metabonomic analysis was performed using proton nuclear magnetic resonance (1H NMR) spectroscopy. RESULTS Microbiomic analysis demonstrated a reduction in alpha diversity (Shannon index) between samples taken at baseline and three days following bowel cleansing (p = 0.002), and there was no significant difference between samples at baseline and six weeks post colonoscopy. Targeted and non-targeted analysis of urinary and faecal bacterial associated metabolites showed no significant impact following bowel cleansing. CONCLUSIONS Bowel cleansing causes a temporary disturbance in bacterial alpha diversity measured in faeces, but no significant changes in the faecal and urine metabolic profiles, suggesting that overall the faecal microbiome and its associated metabolome is resistant to the effects of an induced osmotic diarrhoea.
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Affiliation(s)
- Sam T. R. Powles
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - Kate I. Gallagher
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - Leo W. L. Chong
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - James L. Alexander
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - Benjamin H. Mullish
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - Lucy C. Hicks
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - Julie A. K. McDonald
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- MRC Centre for Molecular Bacteriology and Infection, Flowers Building, Imperial College London, London, SW7 2AZ UK
| | - Julian R. Marchesi
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - Horace R. T. Williams
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
| | - Timothy R. Orchard
- Department of Metabolism, Digestion and Reproduction, Imperial College London, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
- Department of Gastroenterology, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, Praed Street, London, W2 1NY UK
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Distinct Urinary Metabolic Biomarkers of Human Colorectal Cancer. DISEASE MARKERS 2022; 2022:1758113. [PMID: 35521635 PMCID: PMC9064491 DOI: 10.1155/2022/1758113] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 02/26/2022] [Accepted: 03/08/2022] [Indexed: 11/30/2022]
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high mortality rate due to its poor diagnosis in the early stage. Here, we report a urinary metabolomic study on a cohort of CRC patients (n =67) and healthy controls (n =21) using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Pathway analysis showed that a series of pathways that belong to amino acid metabolism, carbohydrate metabolism, and lipid metabolism were dysregulated, for instance the glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glycolysis, and TCA cycle. A total of 48 differential metabolites were identified in CRC compared to controls. A panel of 12 biomarkers composed of chenodeoxycholic acid, vanillic acid, adenosine monophosphate, glycolic acid, histidine, azelaic acid, hydroxypropionic acid, glycine, 3,4-dihydroxymandelic acid, 4-hydroxybenzoic acid, oxoglutaric acid, and homocitrulline were identified by Random Forest (RF), Support Vector Machine (SVM), and Boruta analysis classification model and validated by Gradient Boosting (GB), Logistic Regression (LR), and Random Forest diagnostic model, which were able to discriminate CRC subjects from healthy controls. These urinary metabolic biomarkers provided a novel and promising molecular approach for the early diagnosis of CRC.
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Chen Y, Li EM, Xu LY. Guide to Metabolomics Analysis: A Bioinformatics Workflow. Metabolites 2022; 12:357. [PMID: 35448542 PMCID: PMC9032224 DOI: 10.3390/metabo12040357] [Citation(s) in RCA: 108] [Impact Index Per Article: 36.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/12/2022] [Accepted: 04/14/2022] [Indexed: 02/05/2023] Open
Abstract
Metabolomics is an emerging field that quantifies numerous metabolites systematically. The key purpose of metabolomics is to identify the metabolites corresponding to each biological phenotype, and then provide an analysis of the mechanisms involved. Although metabolomics is important to understand the involved biological phenomena, the approach's ability to obtain an exhaustive description of the processes is limited. Thus, an analysis-integrated metabolomics, transcriptomics, proteomics, and other omics approach is recommended. Such integration of different omics data requires specialized statistical and bioinformatics software. This review focuses on the steps involved in metabolomics research and summarizes several main tools for metabolomics analyses. We also outline the most abnormal metabolic pathways in several cancers and diseases, and discuss the importance of multi-omics integration algorithms. Overall, our goal is to summarize the current metabolomics analysis workflow and its main analysis software to provide useful insights for researchers to establish a preferable pipeline of metabolomics or multi-omics analysis.
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Affiliation(s)
- Yang Chen
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China
- Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
| | - Li-Yan Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041,
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di Meo NA, Loizzo D, Pandolfo SD, Autorino R, Ferro M, Porta C, Stella A, Bizzoca C, Vincenti L, Crocetto F, Tataru OS, Rutigliano M, Battaglia M, Ditonno P, Lucarelli G. Metabolomic Approaches for Detection and Identification of Biomarkers and Altered Pathways in Bladder Cancer. Int J Mol Sci 2022; 23:ijms23084173. [PMID: 35456991 PMCID: PMC9030452 DOI: 10.3390/ijms23084173] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 04/05/2022] [Accepted: 04/08/2022] [Indexed: 12/24/2022] Open
Abstract
Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a “signature pathway” associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.
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Affiliation(s)
- Nicola Antonio di Meo
- Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, Italy; (N.A.d.M.); (D.L.); (M.R.); (M.B.); (P.D.)
| | - Davide Loizzo
- Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, Italy; (N.A.d.M.); (D.L.); (M.R.); (M.B.); (P.D.)
- Division of Urology, Virginia Commonwealth University (VCU) Health, Richmond, VA 23298, USA; (S.D.P.); (R.A.)
| | - Savio Domenico Pandolfo
- Division of Urology, Virginia Commonwealth University (VCU) Health, Richmond, VA 23298, USA; (S.D.P.); (R.A.)
- Division of Urology, University of Naples “Federico II”, 80100 Naples, Italy
| | - Riccardo Autorino
- Division of Urology, Virginia Commonwealth University (VCU) Health, Richmond, VA 23298, USA; (S.D.P.); (R.A.)
| | - Matteo Ferro
- Division of Urology, European Institute of Oncology (IEO), IRCCS, 20141 Milan, Italy;
| | - Camillo Porta
- Department of Biomedical Sciences and Human Oncology, University of Bari, 70124 Bari, Italy; (C.P.); (A.S.)
| | - Alessandro Stella
- Department of Biomedical Sciences and Human Oncology, University of Bari, 70124 Bari, Italy; (C.P.); (A.S.)
| | - Cinzia Bizzoca
- Department of General Surgery “Ospedaliera”, Polyclinic Hospital of Bari, 70124 Bari, Italy; (C.B.); (L.V.)
| | - Leonardo Vincenti
- Department of General Surgery “Ospedaliera”, Polyclinic Hospital of Bari, 70124 Bari, Italy; (C.B.); (L.V.)
| | - Felice Crocetto
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples “Federico II”, 80131 Naples, Italy;
| | - Octavian Sabin Tataru
- I.O.S.U.D., George Emil Palade University of Medicine and Pharmacy, Science and Technology, 540142 Targu Mures, Romania;
| | - Monica Rutigliano
- Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, Italy; (N.A.d.M.); (D.L.); (M.R.); (M.B.); (P.D.)
| | - Michele Battaglia
- Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, Italy; (N.A.d.M.); (D.L.); (M.R.); (M.B.); (P.D.)
| | - Pasquale Ditonno
- Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, Italy; (N.A.d.M.); (D.L.); (M.R.); (M.B.); (P.D.)
| | - Giuseppe Lucarelli
- Department of Emergency and Organ Transplantation-Urology, Andrology and Kidney Transplantation Unit, University of Bari, 70124 Bari, Italy; (N.A.d.M.); (D.L.); (M.R.); (M.B.); (P.D.)
- Correspondence:
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Khoshnevisan K, Chehrehgosha M, Conant M, Mohammad Meftah A, Baharifar H, Ejtahed HS, Angoorani P, Gholami M, Sharifi F, Maleki H, Larijani B, Khorramizadeh MR. Interactive relationship between Trp metabolites and gut microbiota: The impact on human pathology of disease. J Appl Microbiol 2022; 132:4186-4207. [PMID: 35304801 DOI: 10.1111/jam.15533] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2021] [Revised: 01/24/2022] [Accepted: 03/17/2022] [Indexed: 11/28/2022]
Abstract
Tryptophan (Trp), an α-amino acid, is the precursor of serotonin (5-hydroxytryptamine, 5-HT), which is involved in a variety of features of metabolic function and human nutrition. Evidence highlights the role of Trp metabolites (exclusively 5-HT) in the gastrointestinal (GI) tract; however, the mechanisms of action involved in the release of 5-HT in the GI tract are still unknown. Considering the fact that variations of 5-HT may facilitate the growth of certain GI disorders, gaining a better understanding of the function and release of 5-HT in the GI tract would be beneficial. Additionally, investigating Trp metabolism may clarify the relationship between Trp and gut microbiota. It is believed that other metabolites of Trp (mostly that of the kynurenine pathway) may play a significant role in controlling gut microbiota function. In this review, we have attempted to summarize the current research investigating the relationship of gut microbiota, Trp, and 5-HT metabolism (with particular attention paid to their metabolite type, as well as a discussion of the research methods used in each study). Taking together, regarding the role that Trp/5-HT plays in a range of physical and mental diseases, the gut bacterial types, as well as the related disorders, have been exclusively considered.
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Affiliation(s)
- Kamyar Khoshnevisan
- Medical Nanotechnology and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.,Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Chehrehgosha
- Department of Surgical Technology, Paramedical School, Golestan University of Medical Sciences, Gorgan, Iran.,Department of Gerontology, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
| | - Melissa Conant
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, USA
| | - Amir Mohammad Meftah
- Department of Psychiatry, New York State Psychiatric Institute, Columbia University, New York, NY, USA
| | - Hadi Baharifar
- Department of Medical Nanotechnology, Applied Biophotonics Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Hanieh-Sadat Ejtahed
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.,Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Pooneh Angoorani
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Morteza Gholami
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farshad Sharifi
- Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hassan Maleki
- Nano Drug Delivery Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Khorramizadeh
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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30
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Li Z, Deng X, Luo J, Lei Y, Jin X, Zhu J, Lv G. Metabolomic Comparison of Patients With Colorectal Cancer at Different Anticancer Treatment Stages. Front Oncol 2022; 11:574318. [PMID: 35186705 PMCID: PMC8855116 DOI: 10.3389/fonc.2021.574318] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Accepted: 11/05/2021] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND The difficulties of early diagnosis of colorectal cancer (CRC) result in a high mortality rate. The ability to predict the response of a patient to surgical resection or chemotherapy may be of great value for clinicians when planning CRC treatments. Metabolomics is an emerging tool for biomarker discovery in cancer research. Previous reports have indicated that the metabolic profile of individuals can be significantly altered between CRC patients and healthy controls. However, metabolic changes in CRC patients at different treatment stages have not been explored. METHODS To this end, we performed nuclear magnetic resonance (NMR)-based metabolomic analysis to determine metabolite aberrations in CRC patients before and after surgical resection or chemotherapy. In general, a total of 106 urine samples from four clinical groups, namely, healthy volunteers (n = 31), presurgery CRC patients (n = 25), postsurgery CRC patients (n = 25), and postchemotherapy CRC patients (n = 25), were collected and subjected to further analysis. RESULTS In the present study, we identified five candidate metabolites, namely, N-phenylacetylglycine, succinate, 4-hydroxyphenylacetate, acetate, and arabinose, in CRC patients compared with healthy individuals, three of which were reported for the first time. Furthermore, approximately ten metabolites were uniquely identified at each stage of CRC treatment, serving as good candidates for biomarker panel selection. CONCLUSION In summary, these potential metabolite candidates may provide promising early diagnostic and monitoring approaches for CRC patients at different anticancer treatment stages.
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Affiliation(s)
| | | | | | | | | | | | - Guoqing Lv
- Department of Gastroinerstinal Surgery, Peking University Shenzhen Hospital, Shenzhen, China
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Eroglu EC, Kucukgoz Gulec U, Vardar MA, Paydas S. GC-MS based metabolite fingerprinting of serous ovarian carcinoma and benign ovarian tumor. EUROPEAN JOURNAL OF MASS SPECTROMETRY (CHICHESTER, ENGLAND) 2022; 28:12-24. [PMID: 35503418 DOI: 10.1177/14690667221098520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
The aim of this study is to identify urinary metabolomic profile of benign and malign ovarian tumors patients. Samples were analyzed using gas chromatography-mass spectrometry (GC-MS) and metabolomic tools to define biomarkers that cause differentiation between groups. 7 metabolites were found to be different in patients with ovarian cancer (OC) and benign tumors (BT). R2Y and Q2 values were found to be 0.670 and 0.459, respectively. L-tyrosine, glycine, stearic acid, turanose and L-threonine metabolites were defined as prominent biomarkers. The sensitivity of the model was calculated as 90.72% and the specificity as 82.09%. In the pathway analysis, glutathione metabolism, aminoacyl-tRNA biosynthesis, glycine serine and threonine metabolic pathway, primary bile acid biosynthesis pathways were found to be important. According to the t-test, 29 metabolites were found to be significant in urine samples of OC patients and healthy controls (HC). R2Y and Q2 values were found to be 0.8170 and 0.749, respectively. These results showed that the model has high compatibility and predictive power. Benzoic acid, L-threonine, L-pyroglutamic acid, creatinine and 3,4-dihydroxyphenylacetic acid metabolites were determined as prominent biomarkers. The sensitivity of the model was calculated as 93.81% and the specificity as 98.59%. Glycine serine and threonine metabolic pathway, glutathione metabolism and aminoacyl-tRNA biosynthesis pathways were determined important in OC patients and HC. The R2Y, Q2, sensitivity and specificity values in the urine samples of BT patients and HC were found to be 0.869, 0.794, 91.75, 97.01% and 97.18%, respectively. L-threonine, L-pyroglutamic acid, benzoic acid, creatinine and pentadecanol metabolites were determined as prominent biomarkers. Valine, leucine and isoleucine biosynthesis and aminoacyl-tRNA biosynthesis were significant. In this study, thanks to the untargeted metabolomic approach and chemometric methods, every group was differentiated from the others and prominent biomarkers were determined.
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Affiliation(s)
| | - Umran Kucukgoz Gulec
- Medical Faculty, Department of Gynecological Oncology, 63988Cukurova University, Adana, Turkey
| | - Mehmet Ali Vardar
- Medical Faculty, Department of Gynecological Oncology, 63988Cukurova University, Adana, Turkey
| | - Semra Paydas
- Medical Faculty, Department of Oncology, 63988Cukurova University, Adana, Turkey
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32
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Sousa AP, Cunha DM, Franco C, Teixeira C, Gojon F, Baylina P, Fernandes R. Which Role Plays 2-Hydroxybutyric Acid on Insulin Resistance? Metabolites 2021; 11:metabo11120835. [PMID: 34940595 PMCID: PMC8703345 DOI: 10.3390/metabo11120835] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/18/2021] [Accepted: 11/24/2021] [Indexed: 02/08/2023] Open
Abstract
Type 2 Diabetes Mellitus (T2D) is defined as a chronic condition caused by beta cell loss and/or dysfunction and insulin resistance (IR). The discovering of novel biomarkers capable of identifying T2D and other metabolic disorders associated with IR in a timely and accurate way is critical. In this review, 2-hydroxybutyric acid (2HB) is presented as that upheaval biomarker with an unexplored potential ahead. Due to the activation of other metabolic pathways during IR, 2HB is synthesized as a coproduct of protein metabolism, being the progression of IR intrinsically related to the increasing of 2HB levels. Hence, the focus of this review will be on the 2HB metabolite and its involvement in glucose homeostasis. A literature review was conducted, which comprised an examination of publications from different databases that had been published over the previous ten years. A total of 19 articles fulfilled the intended set of criteria. The use of 2HB as an early indicator of IR was separated into subjects based on the number of analytes examined simultaneously. In terms of the association between 2HB and IR, it has been established that increasing 2HB levels can predict the development of IR. Thus, 2HB has demonstrated considerable promise as a clinical monitoring molecule, not only as an IR biomarker, but also for disease follow-up throughout IR treatment.
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Affiliation(s)
- André P. Sousa
- Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lobão Vital 172, 4200-374 Porto, Portugal; (A.P.S.); (C.T.); (F.G.); (P.B.)
- School of Health (ESS), Polytechnic Institute of Porto (IPP), R. António Bernardino de Almeida 400, 4200-072 Porto, Portugal; (D.M.C.); (C.F.)
- Faculty of Medicine, Porto University (FMUP), Alameda Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Diogo M. Cunha
- School of Health (ESS), Polytechnic Institute of Porto (IPP), R. António Bernardino de Almeida 400, 4200-072 Porto, Portugal; (D.M.C.); (C.F.)
| | - Carolina Franco
- School of Health (ESS), Polytechnic Institute of Porto (IPP), R. António Bernardino de Almeida 400, 4200-072 Porto, Portugal; (D.M.C.); (C.F.)
| | - Catarina Teixeira
- Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lobão Vital 172, 4200-374 Porto, Portugal; (A.P.S.); (C.T.); (F.G.); (P.B.)
- School of Health (ESS), Polytechnic Institute of Porto (IPP), R. António Bernardino de Almeida 400, 4200-072 Porto, Portugal; (D.M.C.); (C.F.)
| | - Frantz Gojon
- Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lobão Vital 172, 4200-374 Porto, Portugal; (A.P.S.); (C.T.); (F.G.); (P.B.)
- School of Health (ESS), Polytechnic Institute of Porto (IPP), R. António Bernardino de Almeida 400, 4200-072 Porto, Portugal; (D.M.C.); (C.F.)
- Faculty of Medicine, Porto University (FMUP), Alameda Hernâni Monteiro, 4200-319 Porto, Portugal
| | - Pilar Baylina
- Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lobão Vital 172, 4200-374 Porto, Portugal; (A.P.S.); (C.T.); (F.G.); (P.B.)
- School of Health (ESS), Polytechnic Institute of Porto (IPP), R. António Bernardino de Almeida 400, 4200-072 Porto, Portugal; (D.M.C.); (C.F.)
| | - Ruben Fernandes
- Laboratory of Medical & Industrial Biotechnology (LABMI), Porto Research, Technology & Innovation Center (PORTIC), R. Arquitecto Lobão Vital 172, 4200-374 Porto, Portugal; (A.P.S.); (C.T.); (F.G.); (P.B.)
- School of Health (ESS), Polytechnic Institute of Porto (IPP), R. António Bernardino de Almeida 400, 4200-072 Porto, Portugal; (D.M.C.); (C.F.)
- Correspondence:
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Gouzerh F, Bessière JM, Ujvari B, Thomas F, Dujon AM, Dormont L. Odors and cancer: Current status and future directions. Biochim Biophys Acta Rev Cancer 2021; 1877:188644. [PMID: 34737023 DOI: 10.1016/j.bbcan.2021.188644] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/22/2021] [Accepted: 10/23/2021] [Indexed: 02/07/2023]
Abstract
Cancer is the second leading cause of death in the world. Because tumors detected at early stages are easier to treat, the search for biomarkers-especially non-invasive ones-that allow early detection of malignancies remains a central goal to reduce cancer mortality. Cancer, like other pathologies, often alters body odors, and much has been done by scientists over the last few decades to assess the value of volatile organic compounds (VOCs) as signatures of cancers. We present here a quantitative review of 208 studies carried out between 1984 and 2020 that explore VOCs as potential biomarkers of cancers. We analyzed the main findings of these studies, listing and classifying VOCs related to different cancer types while considering both sampling methods and analysis techniques. Considering this synthesis, we discuss several of the challenges and the most promising prospects of this research direction in the war against cancer.
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Affiliation(s)
- Flora Gouzerh
- CREEC/CANECEV (CREES), Montpellier, France; MIVEGEC, Université de Montpellier, CNRS, IRD, Montpellier, France; CEFE, Univ Montpellier, CNRS, EPHE, IRD, Univ Paul Valéry Montpellier 3, Montpellier, France.
| | - Jean-Marie Bessière
- Ecole Nationale de Chimie de Montpellier, Laboratoire de Chimie Appliquée, Montpellier, France
| | - Beata Ujvari
- Deakin University, School of Life and Environmental Sciences, Centre for Integrative Ecology, Waurn Ponds, Vic 3216, Australia
| | - Frédéric Thomas
- CREEC/CANECEV (CREES), Montpellier, France; MIVEGEC, Université de Montpellier, CNRS, IRD, Montpellier, France
| | - Antoine M Dujon
- CREEC/CANECEV (CREES), Montpellier, France; MIVEGEC, Université de Montpellier, CNRS, IRD, Montpellier, France; Deakin University, School of Life and Environmental Sciences, Centre for Integrative Ecology, Waurn Ponds, Vic 3216, Australia
| | - Laurent Dormont
- CEFE, Univ Montpellier, CNRS, EPHE, IRD, Univ Paul Valéry Montpellier 3, Montpellier, France
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34
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Jiang CH, Lin PF, Chen FC, Chen JY, Xie WJ, Li M, Hu XJ, Chen WL, Cheng Y, Lin XX. Metabolic Profiling Revealed Prediction Biomarkers for Infantile Hemangioma in Umbilical Cord Blood Sera: A Prospective Study. J Proteome Res 2021; 21:822-832. [PMID: 34319108 DOI: 10.1021/acs.jproteome.1c00430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Infantile hemangioma (IH), the most common benign tumor in infancy, mostly arises and has rapid growth before 3 months of age. Because irreversible skin changes occur in the early proliferative stage, early medical treatment is essential to reduce the permanent sequelae caused by IH. Yet there are still no early screening biomarkers for IH before its visible emergence. This study aimed to explore prediction biomarkers using noninvasive umbilical cord blood (UCB). A prospective study of the metabolic profiling approach was performed on UCB sera from 28 infants with IH and 132 matched healthy controls from a UCB population comprising over 1500 infants (PeptideAtlas: PASS01675) using liquid chromatography-mass spectrometry. The metabolic profiling results exhibited the characteristic metabolic aberrance of IH. Machine learning suggested a panel of biomarkers to predict the occurrence of IH, with the area under curve (AUC) values in the receiver operating characteristic analysis all >0.943. Phenylacetic acid had potential to predict infants with large IH (diameter >2 cm) from those with small IH (diameter <2 cm), with an AUC of 0.756. The novel biomarkers in noninvasive UCB sera for predicting IH before its emergence might lead to a revolutionary clinical utility.
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Affiliation(s)
- Cheng-Hong Jiang
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China.,Department of Plastic Surgery and Regenerative Medicine Institute, Fujian Medical University, Fuzhou 35001, China.,Tissue and Organ Regeneration Engineering Center of Fujian Higher Education, Fuzhou 350001, China
| | - Peng-Fei Lin
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Fa-Chun Chen
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Jia-Yao Chen
- Department of Plastic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 51000, China
| | - Wen-Jun Xie
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Ming Li
- Department of Plastic Surgery, Fujian Medical University Union Hospital, Fuzhou 350001, China
| | - Xiao-Jie Hu
- Department of Plastic and Reconstruction Surgery, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200010, China
| | - Wen-Lian Chen
- Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
| | - Yu Cheng
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.,School of Pharmacy, Shanghai Jiao Tong University Shanghai, 200240, China
| | - Xiao-Xi Lin
- Department of Plastic and Reconstruction Surgery, School of Medicine, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University, Shanghai 200010, China
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Chumachenko MS, Waseem TV, Fedorovich SV. Metabolomics and metabolites in ischemic stroke. Rev Neurosci 2021; 33:181-205. [PMID: 34213842 DOI: 10.1515/revneuro-2021-0048] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2021] [Accepted: 06/09/2021] [Indexed: 12/27/2022]
Abstract
Stroke is a major reason for disability and the second highest cause of death in the world. When a patient is admitted to a hospital, it is necessary to identify the type of stroke, and the likelihood for development of a recurrent stroke, vascular dementia, and depression. These factors could be determined using different biomarkers. Metabolomics is a very promising strategy for identification of biomarkers. The advantage of metabolomics, in contrast to other analytical techniques, resides in providing low molecular weight metabolite profiles, rather than individual molecule profiles. Technically, this approach is based on mass spectrometry and nuclear magnetic resonance. Furthermore, variations in metabolite concentrations during brain ischemia could alter the principal neuronal functions. Different markers associated with ischemic stroke in the brain have been identified including those contributing to risk, acute onset, and severity of this pathology. In the brain, experimental studies using the ischemia/reperfusion model (IRI) have shown an impaired energy and amino acid metabolism and confirmed their principal roles. Literature data provide a good basis for identifying markers of ischemic stroke and hemorrhagic stroke and understanding metabolic mechanisms of these diseases. This opens an avenue for the successful use of identified markers along with metabolomics technologies to develop fast and reliable diagnostic tools for ischemic and hemorrhagic stroke.
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Affiliation(s)
- Maria S Chumachenko
- Department of Biochemistry, Faculty of Biology, Belarusian State University, Kurchatova St., 10, Minsk220030, Belarus
| | | | - Sergei V Fedorovich
- Department of Biochemistry, Faculty of Biology, Belarusian State University, Kurchatova St., 10, Minsk220030, Belarus
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Zhu H, Zhou J, Wang D, Yu Z, Li B, Ni Y, He K. Quantitative proteomic analysis reveals that serine/threonine kinase is involved in Streptococcus suis virulence and adaption to stress conditions. Arch Microbiol 2021; 203:4715-4726. [PMID: 34028569 PMCID: PMC8141825 DOI: 10.1007/s00203-021-02369-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 05/06/2021] [Accepted: 05/08/2021] [Indexed: 12/27/2022]
Abstract
The eukaryotic-type serine/threonine kinase of Streptococcus suis serotype 2 (SS2) performs critical roles in bacterial pathogenesis. In this study, isobaric tags for relative and absolute quantification (iTRAQ) MS/MS were used to analyze the protein profiles of wild type strain SS2-1 and its isogenic STK deletion mutant (Δstk). A total of 281 significant differential proteins, including 147 up-regulated and 134 down-regulated proteins, were found in Δstk. Moreover, 69 virulence factors (VFs) among these 281 proteins were predicted by the Virulence Factor Database (VFDB), including 38 downregulated and 31 up-regulated proteins in Δstk, among which 15 down regulated VFs were known VFs of SS2. Among the down-regulated proteins, high temperature requirement A (HtrA), glutamine synthase (GlnA), ferrichrome ABC transporter substrate-binding protein FepB, and Zinc-binding protein AdcA are known to be involved in bacterial survival and/or nutrient and energy acquisition under adverse host conditions. Overall, our results indicate that STK regulates the expression of proteins involved in virulence of SS2 and its adaption to stress environments.
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Affiliation(s)
- Haodan Zhu
- Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, People's Republic of China
- Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, People's Republic of China
| | - Junming Zhou
- Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, People's Republic of China
- Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, People's Republic of China
| | - Dandan Wang
- Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, People's Republic of China
- Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, People's Republic of China
| | - Zhengyu Yu
- Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, People's Republic of China
- Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, People's Republic of China
| | - Bin Li
- Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, People's Republic of China
- Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, People's Republic of China
| | - Yanxiu Ni
- Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China.
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, People's Republic of China.
- Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, People's Republic of China.
| | - Kongwang He
- Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China.
- Jiangsu Co-Innovation Center for the Prevention and Control of Important Animal Infectious Disease and Zoonose, Yangzhou University, Yangzhou, People's Republic of China.
- Key Lab of Food Quality and Safety of Jiangsu Province, State Key Laboratory Breeding Base, Nanjing, People's Republic of China.
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Mallafré-Muro C, Llambrich M, Cumeras R, Pardo A, Brezmes J, Marco S, Gumà J. Comprehensive Volatilome and Metabolome Signatures of Colorectal Cancer in Urine: A Systematic Review and Meta-Analysis. Cancers (Basel) 2021; 13:2534. [PMID: 34064065 PMCID: PMC8196698 DOI: 10.3390/cancers13112534] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 05/13/2021] [Accepted: 05/17/2021] [Indexed: 01/22/2023] Open
Abstract
To increase compliance with colorectal cancer screening programs and to reduce the recommended screening age, cheaper and easy non-invasiveness alternatives to the fecal immunochemical test should be provided. Following the PRISMA procedure of studies that evaluated the metabolome and volatilome signatures of colorectal cancer in human urine samples, an exhaustive search in PubMed, Web of Science, and Scopus found 28 studies that met the required criteria. There were no restrictions on the query for the type of study, leading to not only colorectal cancer samples versus control comparison but also polyps versus control and prospective studies of surgical effects, CRC staging and comparisons of CRC with other cancers. With this systematic review, we identified up to 244 compounds in urine samples (3 shared compounds between the volatilome and metabolome), and 10 of them were relevant in more than three articles. In the meta-analysis, nine studies met the criteria for inclusion, and the results combining the case-control and the pre-/post-surgery groups, eleven compounds were found to be relevant. Four upregulated metabolites were identified, 3-hydroxybutyric acid, L-dopa, L-histidinol, and N1, N12-diacetylspermine and seven downregulated compounds were identified, pyruvic acid, hydroquinone, tartaric acid, and hippuric acid as metabolites and butyraldehyde, ether, and 1,1,6-trimethyl-1,2-dihydronaphthalene as volatiles.
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Affiliation(s)
- Celia Mallafré-Muro
- Department of Electronics and Biomedical Engineering, University of Barcelona, 08028 Barcelona, Spain; (C.M.-M.); (A.P.); (S.M.)
- Signal and Information Processing for Sensing Systems Group, Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
| | - Maria Llambrich
- Metabolomics Interdisciplinary Group (MiL@b), Department of Electrical Electronic Engineering and Automation, Universitat Rovira i Virgili (URV), IISPV, CERCA, 43007 Tarragona, Spain; (M.L.); (J.B.)
| | - Raquel Cumeras
- Metabolomics Interdisciplinary Group (MiL@b), Department of Electrical Electronic Engineering and Automation, Universitat Rovira i Virgili (URV), IISPV, CERCA, 43007 Tarragona, Spain; (M.L.); (J.B.)
- Biomedical Research Centre, Diabetes and Associated Metabolic Disorders (CIBERDEM), ISCIII, 28029 Madrid, Spain
- Fiehn Lab, NIH West Coast Metabolomics Center, University of California Davis, Davis, CA 95616, USA
| | - Antonio Pardo
- Department of Electronics and Biomedical Engineering, University of Barcelona, 08028 Barcelona, Spain; (C.M.-M.); (A.P.); (S.M.)
| | - Jesús Brezmes
- Metabolomics Interdisciplinary Group (MiL@b), Department of Electrical Electronic Engineering and Automation, Universitat Rovira i Virgili (URV), IISPV, CERCA, 43007 Tarragona, Spain; (M.L.); (J.B.)
- Biomedical Research Centre, Diabetes and Associated Metabolic Disorders (CIBERDEM), ISCIII, 28029 Madrid, Spain
| | - Santiago Marco
- Department of Electronics and Biomedical Engineering, University of Barcelona, 08028 Barcelona, Spain; (C.M.-M.); (A.P.); (S.M.)
- Signal and Information Processing for Sensing Systems Group, Institute for Bioengineering of Catalonia, The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain
| | - Josep Gumà
- Oncology Department, Hospital Universitari Sant Joan de Reus, Institut d’Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili (URV), 43204 Reus, Spain;
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Zhou W, Zhu B, Kou F, Qi S, Lv C, Cheng Y, Wei H. Targeted Metabolic Profiling and PRM Analysis of Proteins Revealed Impaired Polyunsaturated Fatty Acid Metabolism and GTP Metabolism in the Brainstem of Spontaneously Hypertensive Rats. J Proteome Res 2021; 20:3305-3314. [PMID: 33999640 DOI: 10.1021/acs.jproteome.1c00208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
An untargeted multi-omics study implicated the potential dysregulation of fatty acid, nucleotide, and energy metabolism in the brainstems of spontaneously hypertensive rats (SHRs). A further quantitative exploration of the alterations in the metabolic pathways is necessary for a deep understanding of the central nervous system in SHRs. Targeted metabolic profiling of 40 fatty acids (PeptideAtlas: PASS01671) and 32 metabolites of nucleotides and energy metabolism (PeptideAtlas: PASS01672) and parallel reaction monitoring analysis of 5 proteins (PeptideAtlas: PASS01673) were performed on the brainstems of SHRs (n = 8, 11 weeks old) and normotensive Wistar rats (n = 8, age-matched) using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem MS. The targeted profiling results of metabolites and proteins revealed decreased polyunsaturated fatty acid (PUFA) synthesis with a significant downregulation of cis-11,14-eicosadienoic acid, cis-13,16-docosadienoic acid, and docosatetraenoate and impaired PUFA oxidation with the accumulation of γ-linolenate induced by the significantly downregulated expression of 2,4-dienoyl-CoA reductase (p < 0.05). Dysregulated GTP and ATP metabolism was observed, with significantly decreased GDP and ADP (p < 0.05) correlated with reduced GTPases of guanine nucleotide-binding protein subunit beta-1 (GNB1), transforming protein RhoA (RHOA), and Rho-related GTP-binding protein RhoB (RHOB) in the brainstem of SHRs. In addition, protein-arginine deiminase type-2 was significantly reduced in the brainstems of SHRs (p < 0.05). The aberrant PUFA and energy metabolism might help to explain the alterations in the brainstem of SHRs. The findings on both metabolites and proteins could provide systemic insights into the pathology basis of altered PUFA and energy metabolism in hypertension, especially in the central nervous system.
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Affiliation(s)
- Wenbin Zhou
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.,Shanghai Zhulian Intelligent Technology Ltd. Co., Shanghai 201323, China
| | - Bangjie Zhu
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.,School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Fang Kou
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Shenglan Qi
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Chunming Lv
- Shanghai Zhulian Intelligent Technology Ltd. Co., Shanghai 201323, China
| | - Yu Cheng
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.,School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China
| | - Hai Wei
- Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Xie G, Wang L, Chen T, Zhou K, Zhang Z, Li J, Sun B, Guo Y, Wang X, Wang Y, Zhang H, Liu P, Nicholson JK, Ge W, Jia W. A Metabolite Array Technology for Precision Medicine. Anal Chem 2021; 93:5709-5717. [PMID: 33797874 DOI: 10.1021/acs.analchem.0c04686] [Citation(s) in RCA: 150] [Impact Index Per Article: 37.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
The application of metabolomics in translational research suffers from several technological bottlenecks, such as data reproducibility issues and the lack of standardization of sample profiling procedures. Here, we report an automated high-throughput metabolite array technology that can rapidly and quantitatively determine 324 metabolites including fatty acids, amino acids, organic acids, carbohydrates, and bile acids. Metabolite identification and quantification is achieved using the Targeted Metabolome Batch Quantification (TMBQ) software, the first cross-vendor data processing pipeline. A test of this metabolite array was performed by analyzing serum samples from patients with chronic liver disease (N = 1234). With high detection efficiency and sensitivity in serum, urine, feces, cell lysates, and liver tissue samples and suitable for different mass spectrometry systems, this metabolite array technology holds great potential for biomarker discovery and high throughput clinical testing. Additionally, data generated from such standardized procedures can be used to generate a clinical metabolomics database suitable for precision medicine in next-generation healthcare.
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Affiliation(s)
- Guoxiang Xie
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.,Human Metabolomics Institute, Inc., Shenzhen, Guangdong 518109, China
| | - Lu Wang
- Human Metabolomics Institute, Inc., Shenzhen, Guangdong 518109, China
| | - Tianlu Chen
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China
| | - Kejun Zhou
- Human Metabolomics Institute, Inc., Shenzhen, Guangdong 518109, China
| | - Zechuan Zhang
- Department of Hepatobiliary Surgery, The Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu 210009, China
| | - Jiufeng Li
- Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China
| | - Beicheng Sun
- Department of Hepatobiliary Surgery, The Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu 210009, China
| | - Yike Guo
- Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China
| | - Xiaoning Wang
- E-Institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Yixing Wang
- E-Institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Hua Zhang
- E-Institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Ping Liu
- E-Institute of Shanghai Municipal Education Committee, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
| | - Jeremy K Nicholson
- Australian National Phenome Center, Health Futures Institute, Murdoch University, Perth, WA 6150, Australia
| | - Weihong Ge
- Department of Pharmacy, The Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School, Nanjing, Jiangsu 210009, China
| | - Wei Jia
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.,Hong Kong Traditional Chinese Medicine Phenome Research Centre, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong 999077, China
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40
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Xiang L, Wu S, Hua Q, Bao C, Liu H. Volatile Organic Compounds in Human Exhaled Breath to Diagnose Gastrointestinal Cancer: A Meta-Analysis. Front Oncol 2021; 11:606915. [PMID: 33747921 PMCID: PMC7970758 DOI: 10.3389/fonc.2021.606915] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 01/21/2021] [Indexed: 12/11/2022] Open
Abstract
Introduction Human exhaled volatile organic compounds (VOCs) are being extensively studied for the purposes of noninvasive cancer diagnoses. This article was primarily to assess the feasibility of utilizing exhaled VOCs analysis for gastrointestinal cancer (GIC) diagnosis. Methods PRISMA-based system searches were conducted for related studies of exhaled VOCs in GIC diagnosis based on predetermined criteria. Relevant articles on colorectal cancer and gastroesophageal cancer were summarized, and meta analysis was performed on articles providing sensitivity and specificity data. Results From 2,227 articles, 14 were found to meet inclusion criteria, six of which were on colorectal cancer (CRC) and eight on Gastroesophageal cancer(GEC). Five articles could provide specific data of sensitivity and specificity in GEC, which were used for meta-analysis. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the curve (AUC) were calculated based on the combination of these data, and were 85.0% [95% confidence interval (CI): 79.0%-90.0%], 89.0% (95%CI: 86.0%-91.0%), 41.30 (21.56-79.10), and 0.93, respectively. Conclusion VOCs can distinguish gastrointestinal cancers from other gastrointestinal diseases, opening up a new avenue for the diagnosis and identification of gastrointestinal cancers, and the analysis of VOCs in exhaled breath has potential clinical application in screening. VOCs are promising tumor biomarkers for GIC diagnosis. Furthermore, limitations like the heterogeneity of diagnostic VOCs between studies should be minded.
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Affiliation(s)
- Lijuan Xiang
- Department of Tumor Biotherapy (5th Ward of the Department of Oncology), Anhui Provincial Cancer Hospital, West District of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.,Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Sihan Wu
- Department of Tumor Biotherapy (5th Ward of the Department of Oncology), Anhui Provincial Cancer Hospital, West District of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.,Department of Oncology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, China
| | - Qingling Hua
- Department of Oncology, Yijishan Hospital, Wannan Medical College, Wuhu, China
| | - Chuyang Bao
- Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Hu Liu
- Department of Tumor Biotherapy (5th Ward of the Department of Oncology), Anhui Provincial Cancer Hospital, West District of The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
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41
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Maurya N, Patel R. Comparative binding analysis of noscapine and piperine with tRNA: A structural perturbation and energetic study. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2021; 247:119089. [PMID: 33126137 DOI: 10.1016/j.saa.2020.119089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/06/2020] [Revised: 10/05/2020] [Accepted: 10/10/2020] [Indexed: 06/11/2023]
Abstract
In this study, we have exploring the binding mechanisms of the two anticancer alkaloid noscapine (NOS) and piperine (PIP) with tRNA using different spectroscopy and computational method. Absorbance and emission spectra revealed that both the drugs show strong binding with tRNA, where NOS intercalate between the base pairs of tRNA and PIP binds in the groove of tRNA. Competitive binding study and steady state anisotropy further confirms the intercalative mode of binding between NOS and tRNA and groove binding in PIP-tRNA complex. The observed thermodynamic parameters suggested that NOS-tRNA complex formation is endothermic and entropy driven, however it was exothermic, and enthalpy driven in case of PIP-tRNA complex. CD and time resolved fluorescence studies show the structural perturbations and conformational change in tRNA structure with NOS as well as PIP. Molecular docking studies are comparable with experimental results and further confirmed that the hydrophobic interactions involved in the NOS-tRNA binding, whereas hydrogen binding and van der Waals interactions play important role in the PIP-tRNA complex formation. This study can be useful to understand the potential binding and resultant tRNA damage by alkaloids and deigned new target specific anticancer drug.
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Affiliation(s)
- Neha Maurya
- Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India
| | - Rajan Patel
- Biophysical Chemistry Laboratory, Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, New Delhi 110025, India.
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Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility. Cancers (Basel) 2021; 13:cancers13030374. [PMID: 33498434 PMCID: PMC7864182 DOI: 10.3390/cancers13030374] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 01/01/2021] [Accepted: 01/14/2021] [Indexed: 01/14/2023] Open
Abstract
The incidence of neuroendocrine neoplasms (NEN) is increasing, but established biomarkers have poor diagnostic and prognostic accuracy. Here, we aim to define the systemic metabolic consequences of NEN and to establish the diagnostic utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) for NEN in a prospective cohort of patients through a single-centre, prospective controlled observational study. Urine samples of 34 treatment-naïve NEN patients (median age: 59.3 years, range: 36-85): 18 had pancreatic (Pan) NEN, of which seven were functioning; 16 had small bowel (SB) NEN; 20 age- and sex-matched healthy control individuals were analysed using a 600 MHz Bruker 1H-NMR spectrometer. Orthogonal partial-least-squares-discriminant analysis models were able to discriminate both PanNEN and SBNEN patients from healthy control (Healthy vs. PanNEN: AUC = 0.90, Healthy vs. SBNEN: AUC = 0.90). Secondary metabolites of tryptophan, such as trigonelline and a niacin-related metabolite were also identified to be universally decreased in NEN patients, while upstream metabolites, such as kynurenine, were elevated in SBNEN. Hippurate, a gut-derived metabolite, was reduced in all patients, whereas other gut microbial co-metabolites, trimethylamine-N-oxide, 4-hydroxyphenylacetate and phenylacetylglutamine, were elevated in those with SBNEN. These findings suggest the existence of a new systems-based neuroendocrine circuit, regulated in part by cancer metabolism, neuroendocrine signalling molecules and gut microbial co-metabolism. Metabonomic profiling of NEN has diagnostic potential and could be used for discovering biomarkers for these tumours. These preliminary data require confirmation in a larger cohort.
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Kumar P, Kumar V. Role of NMR Metabolomics and MR Imaging in Colon Cancer. COLON CANCER DIAGNOSIS AND THERAPY 2021:43-66. [DOI: 10.1007/978-3-030-63369-1_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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Kou F, Zhu B, Zhou W, Lv C, Cheng Y, Wei H. Targeted metabolomics reveals dynamic portrayal of amino acids and derivatives in triple-negative breast cancer cells and culture media. Mol Omics 2020; 17:142-152. [PMID: 33295912 DOI: 10.1039/d0mo00126k] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Triple-negative breast cancer (TNBC) is well-known for its metastatic aggressiveness and poor survival prognosis, accounting for nearly a quarter of cases in breast cancer. We performed intra- and extra-cellular profiling of 40 amino acids and derivatives on three cell lines and their culture media, including TNBC, non-TNBC and normal breast epithelial cells, using HILIC-MS/MS. Characteristic metabolic alteration of amino acids and derivatives was observed in TNBC cells, compared to non-TNBC cells, especially in correlated intra- and extra-cellular metabolic pathways. Intra-cellularly, quantified glutamic acid, β-alanine, aspartic acid, glutathione, N-acetyl-serine and N-acetyl-methionine were most significantly increased (>2-fold, p < 0.01 and VIP > 1) in TNBC cells. Extra-cellularly, significantly increased uptake of glutamine, serine, β-alanine, and lysine and elevated excretion of glutamic acid and l-cysteine-glutathione (p < 0.01 and VIP > 1) were observed by TNBC cells from or to their cell culture media. This study depicted a novel dynamic portrayal of metabolic dysregulation between TNBC and non-TNBC cells, correlated in both intra- and extra-cellular amino acid profiles. Quantification of these distinctive metabolites of TNBC cells might offer advanced understanding and new treatment targets for TNBC.
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Affiliation(s)
- Fang Kou
- Institute of Interdisciplinary Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Lin J, Huang Z, Lin X, Wu Q, Quan K, Cheng Y, Zheng M, Xu J, Dai Y, Qiu H, Lin D, Feng S. Rapid and label-free urine test based on surface-enhanced Raman spectroscopy for the non-invasive detection of colorectal cancer at different stages. BIOMEDICAL OPTICS EXPRESS 2020; 11:7109-7119. [PMID: 33408983 PMCID: PMC7747921 DOI: 10.1364/boe.406097] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 10/29/2020] [Accepted: 11/02/2020] [Indexed: 05/09/2023]
Abstract
The concept of being able to urinate in a cup and screen for colorectal cancer (CRC) is fascinating to the public at large. Here, a simple and label-free urine test based on surface-enhanced Raman spectroscopy (SERS) was employed for CRC detection. Significant spectral differences among normal, stages I-II, and stages III-IV CRC urines were observed. Using discriminant function analysis, the diagnostic sensitivities of 95.8%, 80.9%, and 84.3% for classification of normal, stages I-II, and stages III-IV CRC were achieved in training model, indicating the great promise of urine SERS as a rapid, convenient and noninvasive method for CRC staging detection.
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Affiliation(s)
- Jinyong Lin
- Radiation Oncology Department, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Digital Fujian Internet-of-Things Laboratory of Environment Monitoring, Fujian Normal University, Fuzhou, 350007, China
- These authors contributed equally to this work
| | - Zongwei Huang
- Radiation Oncology Department, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
- These authors contributed equally to this work
| | - Xueliang Lin
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Digital Fujian Internet-of-Things Laboratory of Environment Monitoring, Fujian Normal University, Fuzhou, 350007, China
| | - Qiong Wu
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Digital Fujian Internet-of-Things Laboratory of Environment Monitoring, Fujian Normal University, Fuzhou, 350007, China
| | - Kerun Quan
- School of Nuclear Science and Technology, University of South China, Hengyang 421001, China
| | - Yanming Cheng
- Radiation Oncology Department, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
| | - Mingzhi Zheng
- Radiation Oncology Department, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
| | - Jiaying Xu
- Radiation Oncology Department, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
| | - Yitao Dai
- Radiation Oncology Department, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
| | - Hejin Qiu
- Radiation Oncology Department, Fujian Cancer Hospital & Fujian Medical University Cancer Hospital, Fuzhou, 350014, China
| | - Duo Lin
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Digital Fujian Internet-of-Things Laboratory of Environment Monitoring, Fujian Normal University, Fuzhou, 350007, China
| | - Shangyuan Feng
- Key Laboratory of OptoElectronic Science and Technology for Medicine, Ministry of Education, Fujian Provincial Key Laboratory for Photonics Technology, Digital Fujian Internet-of-Things Laboratory of Environment Monitoring, Fujian Normal University, Fuzhou, 350007, China
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Al Hageh C, Rahy R, Khazen G, Brial F, Khnayzer RS, Gauguier D, Zalloua PA. Plasma and urine metabolomic analyses in aortic valve stenosis reveal shared and biofluid-specific changes in metabolite levels. PLoS One 2020; 15:e0242019. [PMID: 33237940 PMCID: PMC7688110 DOI: 10.1371/journal.pone.0242019] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 10/24/2020] [Indexed: 01/04/2023] Open
Abstract
Aortic valve stenosis (AVS) is a prevalent condition among the elderly population that eventually requires aortic valve replacement. The lack of reliable biomarkers for AVS poses a challenge for its early diagnosis and the application of preventive measures. Untargeted gas chromatography mass spectrometry (GC-MS) metabolomics was applied in 46 AVS cases and 46 controls to identify plasma and urine metabolites underlying AVS risk. Multivariate data analyses were performed on pre-processed data (e.g. spectral peak alignment), in order to detect changes in metabolite levels in AVS patients and to evaluate their performance in group separation and sensitivity of AVS prediction, followed by regression analyses to test for their association with AVS. Through untargeted analysis of 190 urine and 130 plasma features that could be detected and quantified in the GC-MS spectra, we identified contrasting levels of 22 urine and 21 plasma features between AVS patients and control subjects. Following metabolite assignment, we observed significant changes in the concentration of known metabolites in urine (n = 14) and plasma (n = 15) that distinguish the metabolomic profiles of AVS patients from healthy controls. Associations with AVS were replicated in both plasma and urine for about half of these metabolites. Among these, 2-Oxovaleric acid, elaidic acid, myristic acid, palmitic acid, estrone, myo-inositol showed contrasting trends of regulation in the two biofluids. Only trans-Aconitic acid and 2,4-Di-tert-butylphenol showed consistent patterns of regulation in both plasma and urine. These results illustrate the power of metabolomics in identifying potential disease-associated biomarkers and provide a foundation for further studies towards early diagnostic applications in severe heart conditions that may prevent surgery in the elderly.
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Affiliation(s)
- Cynthia Al Hageh
- Université de Paris, INSERM UMRS 1124, Paris, France
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Ryan Rahy
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | - Georges Khazen
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
| | | | - Rony S. Khnayzer
- Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon
- * E-mail: (DG); (RSK); (PAZ)
| | - Dominique Gauguier
- Université de Paris, INSERM UMRS 1124, Paris, France
- McGill University and Genome Quebec Innovation Centre, Montreal, QC, Canada
- * E-mail: (DG); (RSK); (PAZ)
| | - Pierre A. Zalloua
- School of Medicine, University of Balamand, Amioun, Lebanon
- * E-mail: (DG); (RSK); (PAZ)
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Cho S, Song N, Choi JY, Shin A. Effect of Citric Acid Cycle Genetic Variants and Their Interactions with Obesity, Physical Activity and Energy Intake on the Risk of Colorectal Cancer: Results from a Nested Case-Control Study in the UK Biobank. Cancers (Basel) 2020; 12:cancers12102939. [PMID: 33053772 PMCID: PMC7601149 DOI: 10.3390/cancers12102939] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2020] [Revised: 10/04/2020] [Accepted: 10/09/2020] [Indexed: 12/24/2022] Open
Abstract
Simple Summary The citric acid cycle has a central role in the cellular energy metabolism and biosynthesis of macromolecules in the mitochondrial matrix. We identified the single nucleotide polymorphisms (SNPs) of the citrate acid cycle with colorectal cancer susceptibility in UK population. Furthermore, we found the significant interaction of SNPs in the citric acid cycle with the contributors to energy balance and SNP-SNP interactions. Our findings provide clues to the etiology in cancer development related to energy metabolism and evidence on identification of the population at high risk of colorectal cancer. Abstract Colorectal cancer is a common malignancy worldwide. Physical activity and a healthy diet contribute to energy balance and have been recommended for the prevention of colorectal cancer. We suggest that the individual differences in energy balance can be explained by genetic polymorphisms involved in mitochondria, which play a central role in energy metabolism at the cellular level. This study aimed to evaluate the association between genetic variants of the mitochondrial citric acid cycle and colorectal cancer. Study participants comprised 3523 colorectal cancer cases and 10,522 matched controls from the UK Biobank study. Odds ratios (ORs) and 95% confidence intervals (CIs) for colorectal cancer were estimated using a conditional logistic regression model. We found a significant association between the SUCLG2 gene rs35494829 and colon cancer (ORs [95% CIs] per increment of the minor allele, 0.82 [0.74–0.92]). Statistical significance was observed in the interactions of the citric acid cycle variants with obesity, energy intake, and vigorous physical activity in colorectal cancer. We also identified significant SNP-SNP interactions among citric acid cycle SNPs in colorectal cancer. The results of this study may provide evidence for bioenergetics in the development of colorectal cancer and for establishing a precise prevention strategy.
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Affiliation(s)
- Sooyoung Cho
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;
| | - Nan Song
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (N.S.); (J.-Y.C.)
- Department of Epidemiology and Cancer Control, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA
| | - Ji-Yeob Choi
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (N.S.); (J.-Y.C.)
- Department of Biomedical Sciences, Graduate School of Seoul National University, Seoul 03080, Korea
- Medical Research Center, Institute of Health Policy and Management, Seoul National University, Seoul 03080, Korea
| | - Aesun Shin
- Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Korea;
- Cancer Research Institute, Seoul National University, Seoul 03080, Korea; (N.S.); (J.-Y.C.)
- Correspondence: ; Tel.: +82-2-740-8331; Fax: +82-2-747-4830
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Deng Y, Yao H, Chen W, Wei H, Li X, Zhang F, Gao S, Man H, Chen J, Tao X, Li M, Chen W. Profiling of polar urine metabolite extracts from Chinese colorectal cancer patients to screen for potential diagnostic and adverse-effect biomarkers. J Cancer 2020; 11:6925-6938. [PMID: 33123283 PMCID: PMC7592006 DOI: 10.7150/jca.47631] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 08/27/2020] [Indexed: 02/07/2023] Open
Abstract
Background: Metabolomics has demonstrated its potential in the early diagnosis, drug safety evaluation and personalized toxicology research of various cancers. Objectives: We aim to screen for potential diagnostic and capecitabine-related adverse effect (CRAE) biomarkers from urinary endogenous metabolites in Chinese colorectal cancer (CRC) patients. Methods: The metabolic profiles of 139 CRC patients and 50 non-neoplastic controls were analyzed using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry. Results: There were 41 metabolites identified between the CRC patients and the non-neoplastic controls, and 19 metabolites were identified between CRC patients with and without CRAE. Based on these identified metabolites, bioinformatic analysis and prediction model construction were completed. Most of these differential metabolites have important roles in cell proliferation and differentiation and the immune system. Based on binary logistic regression, a CRC prediction model, composed of 3-methylhistidine, N-heptanoylglycine, N1,N12-diacetylspermine and hippurate, was established, with an area under curve (AUC) of 0.980 (95% CI: 0.953-1.000; sensitivity: 94.3%; specificity: 92.0%) in the training set, and an AUC of 0.968 (95% CI: 0.933-1.000; sensitivity: 89.9%; specificity: 92.0%) in the testing set. In addition, methionine and 4-pyridoxic acid can be combined to predict hand foot syndrome, with an AUC of 0.884; ubiquinone-1 and 4-pyridoxic acid can be combined to predict anemia, with an AUC of 0.889; and 5-acetamidovalerate and 3,4-methylenesebacic acid can be combined to predict neutropenia, with an AUC of 0.882. Conclusion: The profiling of urine polar metabolites has great potential in the early detection of CRC and the prediction of CRAE.
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Affiliation(s)
- Yi Deng
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Houshan Yao
- Department of Surgery, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Wei Chen
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Hua Wei
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Xinxing Li
- Department of Surgery, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Feng Zhang
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Shouhong Gao
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Huan Man
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
- College of Chemical and Biological Engineering, Yichun University, Jiangxi Province, China, 336000
| | - Jing Chen
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
- College of Chemical and Biological Engineering, Yichun University, Jiangxi Province, China, 336000
| | - Xia Tao
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Mingming Li
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
| | - Wansheng Chen
- Department of Pharmacy, Changzheng Hospital, Secondary Military Medical University, Shanghai, China, 200003
- Research and Development Center of Chinese Medicine Resources and Biotechnology, Shanghai University of Traditional Chinese Medicine, Shanghai, China, 201203
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49
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A Review of GC-Based Analysis of Non-Invasive Biomarkers of Colorectal Cancer and Related Pathways. J Clin Med 2020; 9:jcm9103191. [PMID: 33019642 PMCID: PMC7601558 DOI: 10.3390/jcm9103191] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 09/27/2020] [Accepted: 09/30/2020] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. In Europe, it is the second most common cause of cancer-related deaths. With the advent of metabolomics approaches, studies regarding the investigation of metabolite profiles related to CRC have been conducted, aiming to serve as a tool for early diagnosis. In order to provide further information about the current status of this field of research, 21 studies were systematically reviewed, regarding their main findings and analytical aspects. A special focus was given to the employment of matrices obtained non-invasively and the use of gas chromatography as the analytical platform. The relationship between the reported volatile and non-volatile biomarkers and CRC-related metabolic alterations was also explored, demonstrating that many of these metabolites are connected with biochemical pathways proven to be involved in carcinogenesis. The most commonly reported CRC indicators were hydrocarbons, aldehydes, amino acids and short-chain fatty acids. These potential biomarkers can be associated with both human and bacterial pathways and the analysis based on such species has the potential to be applied in the clinical practice as a low-cost screening method.
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50
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Sun M, Wu X, Yu Y, Wang L, Xie D, Zhang Z, Chen L, Lu A, Zhang G, Li F. Disorders of Calcium and Phosphorus Metabolism and the Proteomics/Metabolomics-Based Research. Front Cell Dev Biol 2020; 8:576110. [PMID: 33015068 PMCID: PMC7511772 DOI: 10.3389/fcell.2020.576110] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 08/20/2020] [Indexed: 12/19/2022] Open
Abstract
Since calcium and phosphorus play vital roles in a multitude of physiologic systems, disorders of calcium and phosphorus metabolism always lead to severe consequences such as skeletal-related and cardiovascular morbidity, or even life-threatening. Physiologically, the maintenance of calcium and phosphorus homeostasis is achieved via a variety of concerted actions of hormones such as parathyroid hormone (PTH), vitamin D, and fibroblast growth factor (FGF23), which could be regulated mainly at three organs, the intestine, kidney, and bone. Disruption of any organ or factor might lead to disorders of calcium and phosphorus metabolism. Currently, lacking of accurate diagnostic approaches and unknown molecular basis of pathophysiology will result in patients being unable to receive a precise diagnosis and personalized treatment timely. Therefore, it is urgent to identify early diagnostic biomarkers and develop therapeutic strategies. Fortunately, proteomics and metabolomics offer promising tools to discover novel indicators and further understanding of pathological mechanisms. Therefore, in this review, we will give a systematic introduction on PTH-1,25(OH)2D-FGF23 axis in the disorders of calcium and phosphorus metabolism, diagnostic biomarkers identified, and potential altered metabolic pathways involved.
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Affiliation(s)
- Meiheng Sun
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China.,Jiangsu Key Laboratory of Xenotransplantation, School of Basic Medical Science, Nanjing Medical University, Nanjing, China
| | - Xiaoqiu Wu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Yuanyuan Yu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Luyao Wang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Duoli Xie
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong
| | - Zhenlin Zhang
- Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Lin Chen
- Department of Wound Repair and Rehabilitation Medicine, State Key Laboratory of Trauma, Burns and Combined Injury, Trauma Center, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China
| | - Aiping Lu
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China.,Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China.,Institute of Arthritis Research, Shanghai Academy of Chinese Medical Sciences, Shanghai, China
| | - Ge Zhang
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
| | - Fangfei Li
- Law Sau Fai Institute for Advancing Translational Medicine in Bone and Joint Diseases, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Integrated Bioinfomedicine and Translational Science, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tsai, Hong Kong.,Institute of Precision Medicine and Innovative Drug Discovery, HKBU Institute for Research and Continuing Education, Shenzhen, China
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