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Yi Y, Song P, Li Z, Ju J, Sun G, Ren Q, Zhou K, Liu L, Wu HC. Nanopore-based enzyme-linked immunosorbent assay for cancer biomarker detection. NATURE NANOTECHNOLOGY 2025:10.1038/s41565-025-01918-z. [PMID: 40369343 DOI: 10.1038/s41565-025-01918-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2024] [Accepted: 03/25/2025] [Indexed: 05/16/2025]
Abstract
Enzyme-linked immunosorbent assay (ELISA) has been widely used in cancer diagnostics due to its specificity, sensitivity and high throughput. However, conventional ELISA is semiquantitative and has an insufficiently low detection limit for applications requiring ultrahigh sensitivity. In this study, we developed an α-hemolysin-nanopore-based ELISA for detecting cancer biomarkers. After forming the immuno-sandwich complex, peptide probes carrying enzymatic cleavage sites are introduced, where they interact with enzymes conjugated to the detection antibodies within the complex. These probes generate distinct current signatures when translocated through the nanopore after enzymatic cleavage, enabling precise biomarker quantification. This approach offers a low detection limit of up to 0.03 fg ml-1 and the simultaneous detection of six biomarkers, including antigen and antibody biomarkers in blood samples. Overall, the nanopore-based ELISA demonstrates high sensitivity and multiplexing capability, making it suitable for next-generation diagnostic and point-of-care testing applications.
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Affiliation(s)
- Yakun Yi
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Peng Song
- Department of Medical Oncology, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Ziyi Li
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
- University of Chinese Academy of Sciences, Beijing, China
| | - Jinzhou Ju
- University of Chinese Academy of Sciences, Beijing, China
- Beijing National Laboratory for Molecular Sciences, Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
| | - Guixiang Sun
- Department of Laboratory Medicine, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing, China
| | - Qianyuan Ren
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
| | - Ke Zhou
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China
| | - Lei Liu
- College of Food and Bioengineering, Xihua University, Chengdu, China.
| | - Hai-Chen Wu
- Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Beijing, China.
- University of Chinese Academy of Sciences, Beijing, China.
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Wang Y, Ma Z, Li Y, Yang H, Jin J, Jin Y, Zhou G. S9.6 Antibody-Mediated Wireless Portable Biosensor with Multiple Affinity Enhancements for Comprehensive Detection of Nucleic Acid in Serum. Anal Chem 2025; 97:9386-9394. [PMID: 40262093 DOI: 10.1021/acs.analchem.5c00566] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/24/2025]
Abstract
Creating biosensors capable of facilely and entirely excluding the influence of interfering biomolecules in complex samples holds profound significance for advancing detection technology and diagnostics. Here, we develop a wireless portable biosensor (WPB) that prevents interference from abundant biomolecules in serum through homogeneous hybridization and S9.6 antibody-mediated multivalent capture. By transferring the hybridization environment from a heterogeneous chip surface to a homogeneous solution, the biosensor maintains consistent hybridization efficiency in serum as in buffer. Additionally, the use of S9.6 antibody-mediated multivalent capture ensures nearly unchanged binding affinity in serum compared to buffer. On the basis of the multiple affinity enhancements, S9.6 antibody-mediated WPB can achieve ultrasensitive detection of nucleic acid in 50% human serum. Specifically, a subtle blocker is designed to eliminate the competitive monovalent S9.6 antibody-heteroduplex binding, ensuring the efficiency of multivalent S9.6 antibody-heteroduplex interactions. The blocker also enables single-step detection. Moreover, the sensing platform utilizes interferents in serum as in situ antifouling biomolecules to prevent nonspecific adsorption. As a result, the proposed WPB achieves a similar limit of detection for nucleic acids in human serum (95 aM) and in buffer (86 aM). This approach inspires a new idea for complex interference elimination and usage and exhibits comprehensive detection performance in complex samples with potential future diagnostic applications.
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Affiliation(s)
- Yi Wang
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
- Jiaxing Key Laboratory of Molecular Recognition and Sensing, College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China
| | - Zeyu Ma
- Jiaxing Key Laboratory of Molecular Recognition and Sensing, College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China
| | - Yingjing Li
- Jiaxing Key Laboratory of Molecular Recognition and Sensing, College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China
| | - Hongyan Yang
- Jiaxing Key Laboratory of Molecular Recognition and Sensing, College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China
| | - Jia Jin
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
| | - Yuxia Jin
- Department of Prenatal Diagnostic Center, YiWu Maternity and Children Hospital, Jinhua 322015, Zhejiang China
| | - Guobao Zhou
- College of Life Sciences and Medicine, Zhejiang Sci-Tech University, Hangzhou 310018, China
- Jiaxing Key Laboratory of Molecular Recognition and Sensing, College of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China
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Vo DK, Trinh KTL. Polymerase Chain Reaction Chips for Biomarker Discovery and Validation in Drug Development. MICROMACHINES 2025; 16:243. [PMID: 40141854 PMCID: PMC11944077 DOI: 10.3390/mi16030243] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/02/2025] [Revised: 02/17/2025] [Accepted: 02/18/2025] [Indexed: 03/28/2025]
Abstract
Polymerase chain reaction (PCR) chips are advanced, microfluidic platforms that have revolutionized biomarker discovery and validation because of their high sensitivity, specificity, and throughput levels. These chips miniaturize traditional PCR processes for the speed and precision of nucleic acid biomarker detection relevant to advancing drug development. Biomarkers, which are useful in helping to explain disease mechanisms, patient stratification, and therapeutic monitoring, are hard to identify and validate due to the complexity of biological systems and the limitations of traditional techniques. The challenges to which PCR chips respond include high-throughput capabilities coupled with real-time quantitative analysis, enabling researchers to identify novel biomarkers with greater accuracy and reproducibility. More recent design improvements of PCR chips have further expanded their functionality to also include digital and multiplex PCR technologies. Digital PCR chips are ideal for quantifying rare biomarkers, which is essential in oncology and infectious disease research. In contrast, multiplex PCR chips enable simultaneous analysis of multiple targets, therefore simplifying biomarker validation. Furthermore, single-cell PCR chips have made it possible to detect biomarkers at unprecedented resolution, hence revealing heterogeneity within cell populations. PCR chips are transforming drug development, enabling target identification, patient stratification, and therapeutic efficacy assessment. They play a major role in the development of companion diagnostics and, therefore, pave the way for personalized medicine, ensuring that the right patient receives the right treatment. While this tremendously promising technology has exhibited many challenges regarding its scalability, integration with other omics technologies, and conformity with regulatory requirements, many still prevail. Future breakthroughs in chip manufacturing, the integration of artificial intelligence, and multi-omics applications will further expand PCR chip capabilities. PCR chips will not only be important for the acceleration of drug discovery and development but also in raising the bar in improving patient outcomes and, hence, global health care as these technologies continue to mature.
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Affiliation(s)
- Dang-Khoa Vo
- College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of Korea;
| | - Kieu The Loan Trinh
- Bionano Applications Research Center, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Gyeonggi-do, Republic of Korea
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Li Y, Wang L, Chen F, Liao R, Li J, Cao X, Ouyang S, Dai L, Du R. Plasma anti-PRTN3 IgG and IgM autoantibodies: novel biomarkers for early detection of lung adenocarcinoma. Front Immunol 2025; 16:1534078. [PMID: 40028338 PMCID: PMC11868074 DOI: 10.3389/fimmu.2025.1534078] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Accepted: 01/27/2025] [Indexed: 03/05/2025] Open
Abstract
Background Proteinase 3 (PRTN3) has been recognized as a crucial target for anti-neutrophil cytoplasmic autoantibody. However, the relationship between anti-PRTN3 autoantibody and cancer remains largely unexplored. Methods Immunohistochemistry was used to detect the level of PRTN3 in lung adenocarcinoma (LUAD) tissue array. Enzyme-linked immunosorbent assay was conducted to measure anti-PRTN3 IgG and IgM autoantibodies in plasma from patients with early- and advanced-stage LUAD, benign pulmonary nodules (BPN) and normal control (NC). Western blotting and immunofluorescence staining were performed to confirm the presence of plasma immune response to PRTN3. Results PRTN3 protein was highly expressed in LUAD tissues. Elevated plasma levels of anti-PRTN3 IgG and IgM autoantibodies were also detected in LUAD, especially in early LUAD. The AUC of anti-PRTN3 IgG autoantibodies in the diagnosis of early LUAD from NC was 0.782, and from BPN was 0.761. When CEA and anti-PRTN3 autoantibodies were combined, the AUC for the diagnosis of early LUAD was significantly higher than that of CEA alone. The presence of a plasma immune response to PRTN3 in LUAD was also confirmed. Conclusion Anti-PRTN3 IgG and IgM autoantibodies maybe early biomarkers to differentiate LUAD from NC and BPN.
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Affiliation(s)
- Yutong Li
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
| | - Linhong Wang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
| | - Fengqi Chen
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
| | - Rulan Liao
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
| | - Jing Li
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
| | - Xiaobin Cao
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
| | - Songyun Ouyang
- Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory of Tumor Epidemiology & State Key Laboratory of Esophageal Cancer Prevention, Zhengzhou University, Zhengzhou, Henan, China
| | - Renle Du
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan, China
- Beijing Genomics Institution (BGI) College, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Medical Laboratory of Tumor Molecular Biomarkers, Zhengzhou University, Zhengzhou, Henan, China
- Henan Key Laboratory for Pharmacology of Liver Diseases, Zhengzhou University, Zhengzhou, Henan, China
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Leszczynski D. Wireless radiation and health: making the case for proteomics research of individual sensitivity. Front Public Health 2025; 12:1543818. [PMID: 39866356 PMCID: PMC11758280 DOI: 10.3389/fpubh.2024.1543818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Accepted: 12/30/2024] [Indexed: 01/28/2025] Open
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Vo DK, Trinh KTL. Emerging Biomarkers in Metabolomics: Advancements in Precision Health and Disease Diagnosis. Int J Mol Sci 2024; 25:13190. [PMID: 39684900 DOI: 10.3390/ijms252313190] [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: 11/19/2024] [Revised: 12/01/2024] [Accepted: 12/06/2024] [Indexed: 12/18/2024] Open
Abstract
Metabolomics has come to the fore as an efficient tool in the search for biomarkers that are critical for precision health approaches and improved diagnostics. This review will outline recent advances in biomarker discovery based on metabolomics, focusing on metabolomics biomarkers reported in cancer, neurodegenerative disorders, cardiovascular diseases, and metabolic health. In cancer, metabolomics provides evidence for unique oncometabolites that are important for early disease detection and monitoring of treatment responses. Metabolite profiling for conditions such as neurodegenerative and mental health disorders can offer early diagnosis and mechanisms into the disease especially in Alzheimer's and Parkinson's diseases. In addition to these, lipid biomarkers and other metabolites relating to cardiovascular and metabolic disorders are promising for patient stratification and personalized treatment. The gut microbiome and environmental exposure also feature among the influential factors in biomarker discovery because they sculpt individual metabolic profiles, impacting overall health. Further, we discuss technological advances in metabolomics, current clinical applications, and the challenges faced by metabolomics biomarker validation toward precision medicine. Finally, this review discusses future opportunities regarding the integration of metabolomics into routine healthcare to enable preventive and personalized approaches.
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Affiliation(s)
- Dang-Khoa Vo
- College of Pharmacy, Gachon University, 191 Hambakmoe-ro, Yeonsu-gu, Incheon 21936, Republic of Korea
| | - Kieu The Loan Trinh
- BioNano Applications Research Center, Gachon University, 1342 Seongnam-daero, Sujeong-gu, Seongnam-si 13120, Gyeonggi-do, Republic of Korea
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Das A, Nyahatkar S, Sonar S, Kalele K, Subramaniyan V. Unlocking the potential of exosomes: A new frontier in liver cancer liquid biopsy. THE JOURNAL OF LIQUID BIOPSY 2024; 6:100166. [PMID: 40027309 PMCID: PMC11863868 DOI: 10.1016/j.jlb.2024.100166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Revised: 08/30/2024] [Accepted: 09/02/2024] [Indexed: 03/05/2025]
Abstract
Liquid biopsy has emerged as one of the non-invasive diagnostic strategies for cancer, offering significant advantages over traditional tissue biopsies. Exosomes the nanoscale extracellular vesicles, have significantly been in the spotlight of research and investigation as highly informative biomarkers in liquid biopsy. These vesicles, which are secreted by a variety of cells, including tumor cells, contain useful information on the molecular characteristics of the parent cell and could be used as a mirror into the processes underlying cancer biology. The analysis of the biomolecular exosomal cargo, including proteins, nucleic acids, and lipids, has shown great promise for the development of sensitive and specific liquid biopsy-based biomarkers for cancer detection, monitoring, and prognosis. This review discusses the role of exosomes in the liver cancer development and metastatic process, including their ability to transfer oncogenic material and facilitate tumor progression. It also explores the application of exosomes as a tool for early cancer detection, monitoring disease status, and predicting prognosis, with a specific focus on liver cancer. Exosomes hold great promise as a minimally invasive liquid biopsy approach that could revolutionize the way we diagnose and manage this deadly disease.
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Affiliation(s)
- Asmit Das
- Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra, India
| | - Sidhanti Nyahatkar
- Department of Dentistry, VYWS Dental College & Hospital, Amravati, Maharashtra, India
| | - Swarup Sonar
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, India
| | - Ketki Kalele
- Department of Oncology, Neuron Institute of Applied Research, Amravati, Maharashtra, India
| | - Vetriselvan Subramaniyan
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
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Ye C, Lukas H, Wang M, Lee Y, Gao W. Nucleic acid-based wearable and implantable electrochemical sensors. Chem Soc Rev 2024; 53:7960-7982. [PMID: 38985007 PMCID: PMC11308452 DOI: 10.1039/d4cs00001c] [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] [Indexed: 07/11/2024]
Abstract
The rapid advancements in nucleic acid-based electrochemical sensors for implantable and wearable applications have marked a significant leap forward in the domain of personal healthcare over the last decade. This technology promises to revolutionize personalized healthcare by facilitating the early diagnosis of diseases, monitoring of disease progression, and tailoring of individual treatment plans. This review navigates through the latest developments in this field, focusing on the strategies for nucleic acid sensing that enable real-time and continuous biomarker analysis directly in various biofluids, such as blood, interstitial fluid, sweat, and saliva. The review delves into various nucleic acid sensing strategies, emphasizing the innovative designs of biorecognition elements and signal transduction mechanisms that enable implantable and wearable applications. Special perspective is given to enhance nucleic acid-based sensor selectivity and sensitivity, which are crucial for the accurate detection of low-level biomarkers. The integration of such sensors into implantable and wearable platforms, including microneedle arrays and flexible electronic systems, actualizes their use in on-body devices for health monitoring. We also tackle the technical challenges encountered in the development of these sensors, such as ensuring long-term stability, managing the complexity of biofluid dynamics, and fulfilling the need for real-time, continuous, and reagentless detection. In conclusion, the review highlights the importance of these sensors in the future of medical engineering, offering insights into design considerations and future research directions to overcome existing limitations and fully realize the potential of nucleic acid-based electrochemical sensors for healthcare applications.
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Affiliation(s)
- Cui Ye
- Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
| | - Heather Lukas
- Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
| | - Minqiang Wang
- Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
| | - Yerim Lee
- Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
| | - Wei Gao
- Andrew and Peggy Cherng Department of Medical Engineering, Division of Engineering and Applied Science, California Institute of Technology, Pasadena, CA, USA.
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Tan C, Qin G, Wang QQ, Li KM, Zhou YC, Yao SK. Comprehensive serum proteomics profiles and potential protein biomarkers for the early detection of advanced adenoma and colorectal cancer. World J Gastrointest Oncol 2024; 16:2971-2987. [PMID: 39072170 PMCID: PMC11271786 DOI: 10.4251/wjgo.v16.i7.2971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 03/08/2024] [Accepted: 05/15/2024] [Indexed: 07/12/2024] Open
Abstract
BACKGROUND The majority of colorectal cancer (CRC) cases develop from precursor advanced adenoma (AA). With the development of proteomics technologies, blood protein biomarkers have potential applications in the early screening of AA and CRC in the general population. AIM To identify serum protein biomarkers for the early screening of AA and CRC. METHODS We collected 43 serum samples from 8 normal controls (NCs), 19 AA patients and 16 CRC patients at China-Japan Friendship Hospital. Quantitative proteomic analysis was performed using liquid chromatography-mass spectrometry/mass spectrometry and data independent acquisition, and differentially expressed proteins (DEPs) with P-values < 0.05 and absolute fold changes > 1.5 were screened out, followed by bioinformatics analysis. Prognosis was further analyzed based on public databases, and proteins expression in tissues were validated by immunohistochemistry. RESULTS A total of 2132 proteins and 17365 peptides were identified in the serum samples. There were 459 upregulated proteins and 118 downregulated proteins in the NC vs AA group, 289 and 180 in the NC vs CRC group, and 52 and 248 in the AA vs CRC group, respectively. Bioinformatic analysis revealed that these DEPs had different functions and participated in extensive signaling pathways. We also identified DIAPH1, VASP, RAB11B, LBP, SAR1A, TUBGCP5, and DOK3 as important proteins for the progression of AA and CRC. Furthermore, VASP (P < 0.01), LBP (P = 0.01), TUBGCP5 (P < 0.01), and DOK3 (P < 0.01) were associated with a poor prognosis. In addition, we propose that LBP and VASP may be more promising protein biomarkers for the early screening of colorectal tumors. CONCLUSION Our study elucidated the serum proteomic profiles of AA and CRC patients, and the identified proteins, such as LBP and VASP, may contribute to the early detection of AA and CRC.
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Affiliation(s)
- Chang Tan
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Geng Qin
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
| | - Qian-Qian Wang
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Kai-Min Li
- School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China
| | - Yuan-Chen Zhou
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
| | - Shu-Kun Yao
- Graduate School, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China
- Department of Gastroenterology, China-Japan Friendship Hospital, Beijing 100029, China
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Hajab H, Anwar A, Nawaz H, Majeed MI, Alwadie N, Shabbir S, Amber A, Jilani MI, Nargis HF, Zohaib M, Ismail S, Kamal A, Imran M. Surface-enhanced Raman spectroscopy of the filtrate portions of the blood serum samples of breast cancer patients obtained by using 30 kDa filtration device. SPECTROCHIMICA ACTA. PART A, MOLECULAR AND BIOMOLECULAR SPECTROSCOPY 2024; 311:124046. [PMID: 38364514 DOI: 10.1016/j.saa.2024.124046] [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: 12/04/2023] [Revised: 02/04/2024] [Accepted: 02/12/2024] [Indexed: 02/18/2024]
Abstract
Raman spectroscopy is reliable tool for analyzing and exploring early disease diagnosis related to body fluids, such as blood serum, which contain low molecular weight fraction (LMWF) and high molecular weight fraction (HMWF) proteins. The disease biomarkers consist of LMWF which are dominated by HMWF hence their analysis is difficult. In this study, in order to overcome this issue, centrifugal filter devices of 30 kDa were used to obtain filtrate and residue portions obtained from whole blood serum samples of control and breast cancer diagnosed patients. The filtrate portions obtained in this way are expected to contain the marker proteins of breast cancer of the size below this filter size. These may include prolactin, Microphage migration inhabitation factor (MIF), γ-Synuclein, BCSG1, Leptin, MUC1, RS/DJ-1 present in the centrifuged blood serum (filtrate portions) which are then analyzed by the SERS technique to recognize the SERS spectral characteristics associated with the progression of breast cancer in the samples of different stages as compared to the healthy ones. The key intention of this study is to achieve early-stage breast cancer diagnosis through the utilization of Surface Enhanced Raman Spectroscopy (SERS) after the centrifugation of healthy and breast cancer serum samples with Amicon ultra-filter devices of 30 kDa. The silver nanoparticles with high plasmon resonance are used as a substrate for SERS analysis. Principal Component Analysis (PCA) and Partial Least Discriminant Analysis (PLS-DA) models are utilized as spectral classification tools to assess and predict rapid, reliable, and non-destructive SERS-based analysis. Notably, they were particularly effective in distinguishing between different SERS spectral groups of the cancerous and non-cancerous samples. By comparing all these spectral data sets to each other PLSDA shows the 79 % accuracy, 76 % specificity, and 81 % sensitivity in samples with AUC value of AUC = 0.774 SERS has proven to be a valuable technique for the rapid identification of the SERS spectral features of blood serum and its filtrate fractions from both healthy individuals and those with breast cancer, aiding in disease diagnosis.
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Affiliation(s)
- Hawa Hajab
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Ayesha Anwar
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Haq Nawaz
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan.
| | - Muhammad Irfan Majeed
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan.
| | - Najah Alwadie
- Department of Physics, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.
| | - Sana Shabbir
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Arooj Amber
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | | | - Hafiza Faiza Nargis
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Muhammad Zohaib
- Department of Zoology, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Sidra Ismail
- Medical College, Foundation University Islamabad, Pakistan
| | - Abida Kamal
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Muhammad Imran
- Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha, Saudi Arabia
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Shen L, Zhang Z, Wu P, Yang J, Cai Y, Chen K, Chai S, Zhao J, Chen H, Dai X, Yang B, Wei W, Dong L, Chen J, Jiang P, Cao C, Ma C, Xu C, Zou Y, Zhang J, Xiong W, Li Z, Xu S, Shu B, Wang M, Li Z, Wan Q, Xiong N, Chen S. Mechanistic insight into glioma through spatially multidimensional proteomics. SCIENCE ADVANCES 2024; 10:eadk1721. [PMID: 38363834 PMCID: PMC10871530 DOI: 10.1126/sciadv.adk1721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 01/16/2024] [Indexed: 02/18/2024]
Abstract
Characterizing the tumor microenvironment at the molecular level is essential for understanding the mechanisms of tumorigenesis and evolution. However, the specificity of the blood proteome in localized region of the tumor and its linkages with other systems is difficult to investigate. Here, we propose a spatially multidimensional comparative proteomics strategy using glioma as an example. The blood proteome signature of tumor microenvironment was specifically identified by in situ collection of arterial and venous blood from the glioma region of the brain for comparison with peripheral blood. Also, by integrating with different dimensions of tissue and peripheral blood proteomics, the information on the genesis, migration, and exchange of glioma-associated proteins was revealed, which provided a powerful method for tumor mechanism research and biomarker discovery. The study recruited multidimensional clinical cohorts, allowing the proteomic results to corroborate each other, reliably revealing biological processes specific to gliomas, and identifying highly accurate biomarkers.
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Affiliation(s)
- Lei Shen
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhourui Zhang
- The Institute for Advanced Studies, Wuhan University, Wuhan, China
| | - Pengfei Wu
- The Institute for Advanced Studies, Wuhan University, Wuhan, China
| | - Jingyi Yang
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yuankun Cai
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Keyu Chen
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Songshan Chai
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jingwei Zhao
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Hongyu Chen
- The Institute for Advanced Studies, Wuhan University, Wuhan, China
| | - Xuan Dai
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Bangkun Yang
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wei Wei
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Lixin Dong
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jincao Chen
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Pucha Jiang
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Changjun Cao
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Chao Ma
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Chengshi Xu
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Yichun Zou
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Jibo Zhang
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Wenping Xiong
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zhengwei Li
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Shuangxiang Xu
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Bing Shu
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Mengyang Wang
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Zejin Li
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Qiongqiong Wan
- The Institute for Advanced Studies, Wuhan University, Wuhan, China
| | - Nanxiang Xiong
- Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, China
| | - Suming Chen
- The Institute for Advanced Studies, Wuhan University, Wuhan, China
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12
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Meng X, Zuo W, Wu P, Song Y, Yang GJ, Zhang S, Yang J, Zou X, Wei W, Zhang D, Dai J, Ju Y. Bimetallic Nanozyme: A Credible Tag for In Situ-Catalyzed Reporter Deposition in the Lateral Flow Immunoassay for Ultrasensitive Cancer Diagnosis. NANO LETTERS 2024; 24:51-60. [PMID: 37823474 DOI: 10.1021/acs.nanolett.3c03118] [Citation(s) in RCA: 25] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/13/2023]
Abstract
The lateral flow immunoassay (LFIA) is a sought-after point-of-care testing platform, yet the insufficient sensitivity of the LFIA limits its application in the detection of tumor biomarkers. Here, a colorimetric signal amplification method, bimetallic nanozyme-mediated in situ-catalyzed reporter deposition (BN-ISCRD), was designed for ultrasensitive cancer diagnosis. The bimetallic nanozyme used, palladium@iridium core-shell nanoparticles (Pd@Ir NPs), had ultrahigh enzyme-like activity, which was further explained by the electron transfer of Pd@Ir NPs and the change in the Gibbs free energy during catalysis through density functional theory calculations. With gastric cancer biomarkers pepsinogen I and pepsinogen II as model targets, this assay could achieve a cutoff value of 10 pg/mL, which was 200-fold lower than that without signal enhancement. The assay was applied to correctly identify 8 positive and 28 negative clinical samples. Overall, this BN-ISCRD-based LFIA showed great merits and potential in the application of ultrasensitive disease diagnosis.
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Affiliation(s)
- Xiangming Meng
- College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Wanchao Zuo
- College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Pengcheng Wu
- College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Yuhan Song
- Nanjing Institute for Food and Drug Control, Nanjing 210038, China
| | - Gong-Jun Yang
- College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Shibo Zhang
- College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
| | - Jun Yang
- Nanjing Institute for Food and Drug Control, Nanjing 210038, China
| | - Xiaopeng Zou
- Zhanjiang Institute of Clinical Medicine, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang 524045, China
| | - Wenlu Wei
- Zhanjiang Institute of Clinical Medicine, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang 524045, China
| | - Donghui Zhang
- Zhanjiang Institute of Clinical Medicine, Guangdong Medical University Zhanjiang Central Hospital, Zhanjiang 524045, China
| | - Jianjun Dai
- College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
- MOE Joint International Research Laboratory of Animal Health and Food Safety, Key Laboratory of Animal Bacteriology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China
| | - Yanmin Ju
- College of Pharmacy, China Pharmaceutical University, Nanjing 211198, China
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13
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Li Z, Wang D, Zhang W, Shi H, Zhu M. Novel PBMC LncRNA signatures as diagnostic biomarkers for colorectal cancer. Pathol Res Pract 2024; 253:154985. [PMID: 38039742 DOI: 10.1016/j.prp.2023.154985] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2023] [Revised: 10/20/2023] [Accepted: 11/23/2023] [Indexed: 12/03/2023]
Abstract
The expression of long non-coding RNAs (LncRNAs) in peripheral blood mononuclear cell (PBMC) and its clinical relevance in colorectal cancer (CRC) remains largely uncharacterized. To address these gaps, we investigated the expression profiles of lncRNAs in PBMC from CRC and healthy controls (HC) by RNA sequencing. The expression level of differentially expressed lncRNAs (DElncRNAs) were evaluated by quantitative PCR in PBMC samples from CRC patients and HC. A total of 447 DElncRNAs were identified, with 178 elevated lncRNAs and 269 decreased lncRNAs in PBMC from CRC patients as compared with that from HC. RT-PCR results supported a significant elevation of NEAT1:11, lnc-PDZD8-1:5 and LINC00910:16 in 98 CRC patients and 82 HC. The clinical implication of NEAT1:11, lnc-PDZD8-1:5 and LINC00910:16 as CRC diagnostic biomarker were determined by receiver operating characteristic (ROC) curve, showing sensitivity 74.5% and specificity 84.5% for joint detection the three lncRNAs. Notably, NEAT1:11 was closely related with the size and extent of primary tumor, with higher relative expression of NEAT1:11 in higher T stage (P = 0.0047). Moreover, NEAT1:11 was related with grade (P = 0.012). Collectively, PBMC from patients with CRC show significantly variable expression profiles of lncRNAs, and detection of these differential expression lncRNAs may provide useful information for basic and clinical research.
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Affiliation(s)
- Zhaosheng Li
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Dongfeng Wang
- Department of General Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Wenjun Zhang
- Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China
| | - Huina Shi
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Mingchen Zhu
- Department of Clinical Laboratory, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China.
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14
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Wang W, Geng L, Zhang Y, Shen W, Bi M, Gong T, Hu Z, Guo C, Wang T, Sun T. Development of antibody-aptamer sandwich-like immunosensor based on RCA and Nicked-PAM CRISPR/Cas12a system for the ultra-sensitive detection of a biomarker. Anal Chim Acta 2023; 1283:341849. [PMID: 37977804 DOI: 10.1016/j.aca.2023.341849] [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: 09/12/2023] [Revised: 09/22/2023] [Accepted: 09/24/2023] [Indexed: 11/19/2023]
Abstract
Biomarkers are the most sensitive reactants and early indicators of many kinds of diseases. The development of highly sensitive and simple techniques to quantify them is challenging. In this study, based on rolling cycle amplification (RCA) and the Nicked PAM/CRISPR-Cas12a system (RNPC) as a signal reporter, a sandwich-type method was developed using antibody@magnetic beads and aptamer for the high-sensitive detection of the C-reactive protein (CRP). The antibody-antigen (target)-aptamer sandwich-like reaction was coupled to RCA, which can produce hundreds of similar binding sites and are discriminated by CRISPR/Cas12a for signal amplification. The ultrasensitivity is achieved based on the dual-signal enhancing strategy, which involves the special recognition of aptamers, RCA, and trans-cleavage of CRISPR/Cas12a. By incorporating the CRISPR/Cas12a system with cleaved PAM, the nonspecific amplification of the RCA reaction alone was greatly reduced, and the dual signal output of RCA and Cas12a improved the detection sensitivity. Our assay can be performed only in two steps. The first step takes only 20 min of target capture, followed by a one-pot reaction, where the target concentration can be obtained by fluorescence values as long as there are 37 °C reaction conditions. Under optimal conditions, this system detected CRP with high sensitivity. The fabricated biosensor showed detection limits of 0.40 pg/mL in phosphate-buffered saline and 0.73 pg/mL in diluted human serum and a broad linear dynamic range of 1.28 pg/mL to 100 ng/mL within a total readout time of 90 min. The method could be used to perform multi-step signal amplification, which can help in the ultrasensitive detection of other proteins. Overall, the proposed biosensor might be used as an immunosensor biosensor platform.
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Affiliation(s)
- Wen Wang
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China; School of Public Health and Management, Binzhou Medical College, Shandong, 264003, PR China
| | - Lu Geng
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China
| | - Yiyang Zhang
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China
| | - Weili Shen
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China
| | - Meng Bi
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China
| | - Tingting Gong
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China
| | - Zhiyong Hu
- School of Public Health and Management, Binzhou Medical College, Shandong, 264003, PR China
| | - Changjiang Guo
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China; School of Public Health and Management, Binzhou Medical College, Shandong, 264003, PR China.
| | - Tianhui Wang
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China.
| | - Tieqiang Sun
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, PR China.
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15
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Parks CG, Wilson LE, Capello M, Deane KD, Hanash SM. Tumor-Associated and Systemic Autoimmunity in Pre-Clinical Breast Cancer among Post-Menopausal Women. Biomolecules 2023; 13:1566. [PMID: 38002248 PMCID: PMC10669589 DOI: 10.3390/biom13111566] [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: 07/20/2023] [Revised: 10/07/2023] [Accepted: 10/11/2023] [Indexed: 11/26/2023] Open
Abstract
Autoantibodies to tumor-associated antigens (anti-TAA) are potential biomarkers for breast cancer, but their relationship systemic autoimmunity as ascertained though antinuclear antibodies (ANA) is unknown and warrants consideration given the common occurrence of autoimmunity and autoimmune diseases among women. The relationship between anti-TAAs and ANA among women who were later diagnosed with breast cancer and others who remained cancer free in the Women's Health Initiative cohort. The study sample included 145 post-menopausal women with baseline ANA data. A total of 37 ANA-positive women who developed breast cancer (i.e., cases; mean time to diagnosis 6.8 years [SE 3.9]) were matched to a random sample of 36 ANA-negative cases by age and time to diagnosis. An age-matched control sample was selected including 35 ANA-positive and 37 ANA-negative women who did not develop breast cancer (i.e., controls; follow-up time ~13 years [SE 3]). Baseline sera were assessed for Immunoglobulin G (IgG) antibodies, measured by custom microarray for 171 breast and other cancer-associated TAA. We used linear regression to estimate cross-sectional associations of ANA with log-transformed anti-TAA among cases and controls. Most anti-TAA did not vary by ANA status. Two anti-TAA were elevated in ANA-positive compared to ANA-negative cases: anti-PGM3 (p = 0.004) and anti-TTN (p = 0.005, especially in cases up to 7 years before diagnosis, p = 0.002). Anti-TAA antibodies were not generally related to ANA, a common marker of systemic autoimmunity. Associations of ANA with particular antigens inducing autoimmunity prior to breast cancer warrant further investigation.
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Affiliation(s)
- Christine G. Parks
- Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
| | - Lauren E. Wilson
- Center for Population Health, Duke University School of Medicine, Durham, NC 27710, USA
| | - Michela Capello
- Departments of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (S.M.H.)
| | - Kevin D. Deane
- Division of Rheumatology, University of Colorado School of Medicine, Aurora, CO 80045, USA
| | - Samir M. Hanash
- Departments of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA (S.M.H.)
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16
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Zhu Q, He P, Zheng C, Chen Z, Qi S, Zhou D, Li Y, Ouyang Q, Zi H, Tang H, Xing J, Xie Y, Zhu S, Ren J, Huang J. Identification and evaluation of novel serum autoantibody biomarkers for early diagnosis of gastric cancer and precancerous lesion. J Cancer Res Clin Oncol 2023; 149:8369-8378. [PMID: 37079049 DOI: 10.1007/s00432-023-04732-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 03/30/2023] [Indexed: 04/21/2023]
Abstract
PURPOSE Early diagnosis is crucial for optimal prognosis of gastric cancer (GC). Hereby, we aimed to identify novel serum autoantibody-based biomarkers for precancerous lesion (PL) and early GC. METHODS We performed serological proteome analysis (SERPA) combined with nanoliter-liquid chromatography combined with quadrupole time of flight tandem mass spectrometry (Nano-LC-Q-TOF-MS/MS) to screen for GC-associated autoantibodies. The identified autoantibodies were analyzed for potential detection value for PL and GC by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic (ROC) curves analysis was conducted to evaluate the accuracy of the biomarkers. RESULTS We identified seven candidates, such as mRNA export factor (RAE1), Nucleophosmin 1 (NPM1), phosphoglycerate kinase 1 (PGK1), and ADP-ribosylation factor 4 (ARF4). Antibodies against all seven proteins were present at higher levels in sera from 242 patients (51 PL, 78 early GC, 113 advanced GC) compared with sera from 122 healthy individuals. RAE1-specific autoantibody discriminated best between patients at different GC stages, with area under the curve (AUC) values of 0.710, 0.745, and 0.804 for PL, early GC, and advanced GC, respectively. Two predictive models composed of gender, RAE1, PGK1, NPM1, and ARF4 autoantibodies (Model 2 for PL) and of age, gender, RAE1, PGK1, and NPM1 autoantibodies (Model 3 for early GC) had improved diagnostic efficiencies, with AUCs of 0.803 and 0.857, sensitivities of 66.7% and 75.6%, and specificities of 78.7% and 87.7%, respectively. CONCLUSION The identified serum tumor-associated autoantibodies (TAAbs) may have good potential for early detection of GC and PL.
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Affiliation(s)
- Qianyu Zhu
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Pingping He
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Cuiling Zheng
- Department of Clinical Laboratory, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
| | - Zhibin Chen
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Saiping Qi
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Donghu Zhou
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Yanmeng Li
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Qin Ouyang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Huaduan Zi
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Hengcheng Tang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Jie Xing
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Yibin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
| | - Jiansong Ren
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
| | - Jian Huang
- Beijing Institute of Clinical Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
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17
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Birhanu AG. Mass spectrometry-based proteomics as an emerging tool in clinical laboratories. Clin Proteomics 2023; 20:32. [PMID: 37633929 PMCID: PMC10464495 DOI: 10.1186/s12014-023-09424-x] [Citation(s) in RCA: 46] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Accepted: 08/03/2023] [Indexed: 08/28/2023] Open
Abstract
Mass spectrometry (MS)-based proteomics have been increasingly implemented in various disciplines of laboratory medicine to identify and quantify biomolecules in a variety of biological specimens. MS-based proteomics is continuously expanding and widely applied in biomarker discovery for early detection, prognosis and markers for treatment response prediction and monitoring. Furthermore, making these advanced tests more accessible and affordable will have the greatest healthcare benefit.This review article highlights the new paradigms MS-based clinical proteomics has created in microbiology laboratories, cancer research and diagnosis of metabolic disorders. The technique is preferred over conventional methods in disease detection and therapy monitoring for its combined advantages in multiplexing capacity, remarkable analytical specificity and sensitivity and low turnaround time.Despite the achievements in the development and adoption of a number of MS-based clinical proteomics practices, more are expected to undergo transition from bench to bedside in the near future. The review provides insights from early trials and recent progresses (mainly covering literature from the NCBI database) in the application of proteomics in clinical laboratories.
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18
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Al-Sulaiti H, Almaliti J, Naman CB, Al Thani AA, Yassine HM. Metabolomics Approaches for the Diagnosis, Treatment, and Better Disease Management of Viral Infections. Metabolites 2023; 13:948. [PMID: 37623891 PMCID: PMC10456346 DOI: 10.3390/metabo13080948] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Revised: 06/29/2023] [Accepted: 06/30/2023] [Indexed: 08/26/2023] Open
Abstract
Metabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases.
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Affiliation(s)
- Haya Al-Sulaiti
- QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (H.A.-S.); (A.A.A.T.)
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
| | - Jehad Almaliti
- Scripps Institution of Oceanography, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA P.O. Box 92093, USA;
- Department of Pharmaceutical Sciences, College of Pharmacy, The University of Jordan, Amman P.O. Box 11942, Jordan
| | - C. Benjamin Naman
- Department of Science and Conservation, San Diego Botanic Garden, Encinitas, CA P.O. Box 92024, USA;
| | - Asmaa A. Al Thani
- QU Health, Qatar University, Doha P.O. Box 2713, Qatar; (H.A.-S.); (A.A.A.T.)
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- College of Health Sciences, QU-Health, Qatar University, Doha P.O. Box 2713, Qatar
| | - Hadi M. Yassine
- Biomedical Research Center, Qatar University, Doha P.O. Box 2713, Qatar
- College of Health Sciences, QU-Health, Qatar University, Doha P.O. Box 2713, Qatar
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19
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Luna-Ramirez RI, Limesand SW, Goyal R, Pendleton AL, Rincón G, Zeng X, Luna-Nevárez G, Reyna-Granados JR, Luna-Nevárez P. Blood Transcriptomic Analyses Reveal Functional Pathways Associated with Thermotolerance in Pregnant Ewes Exposed to Environmental Heat Stress. Genes (Basel) 2023; 14:1590. [PMID: 37628641 PMCID: PMC10454332 DOI: 10.3390/genes14081590] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/25/2023] [Accepted: 08/03/2023] [Indexed: 08/27/2023] Open
Abstract
Environmental heat stress triggers a series of compensatory mechanisms in sheep that are dependent on their genetic regulation of thermotolerance. Our objective was to identify genes and regulatory pathways associated with thermotolerance in ewes exposed to heat stress. We performed next-generation RNA sequencing on blood collected from 16 pregnant ewes, which were grouped as tolerant and non-tolerant to heat stress according to a physiological indicator. Additional samples were collected to measure complete blood count. A total of 358 differentially expressed genes were identified after applying selection criteria. Gene expression analysis detected 46 GO terms and 52 KEGG functional pathways. The top-three signaling pathways were p53, RIG-I-like receptor and FoxO, which suggested gene participation in biological processes such as apoptosis, cell signaling and immune response to external stressors. Network analysis revealed ATM, ISG15, IRF7, MDM4, DHX58 and TGFβR1 as over-expressed genes with high regulatory potential. A co-expression network involving the immune-related genes ISG15, IRF7 and DXH58 was detected in lymphocytes and monocytes, which was consistent with hematological findings. In conclusion, transcriptomic analysis revealed a non-viral immune mechanism involving apoptosis, which is induced by external stressors and appears to play an important role in the molecular regulation of heat stress tolerance in ewes.
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Affiliation(s)
- Rosa I. Luna-Ramirez
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA
| | - Sean W. Limesand
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA
| | - Ravi Goyal
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA
| | - Alexander L. Pendleton
- School of Animal and Comparative Biomedical Sciences, University of Arizona, Tucson, AZ 85721, USA
| | | | - Xi Zeng
- Zoetis Inc., VMRD Genetics R&D, Kalamazoo, MI 49007, USA
| | - Guillermo Luna-Nevárez
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
| | - Javier R. Reyna-Granados
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
| | - Pablo Luna-Nevárez
- Departamento de Ciencias Agronómicas y Veterinarias, Instituto Tecnológico de Sonora, Ciudad Obregón 85000, Mexico
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20
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Downs BM, Hoang TM, Cope L. Increasing the Capture Rate of Circulating Tumor DNA in Unaltered Plasma Using Passive Microfluidic Mixer Flow Cells. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2023; 39:3225-3234. [PMID: 36811956 DOI: 10.1021/acs.langmuir.2c02919] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
A limiting factor in using blood-based liquid biopsies for cancer detection is the volume of extracted blood required to capture a measurable number of circulating tumor DNA (ctDNA). To overcome this limitation, we developed a technology named the dCas9 capture system to capture ctDNA from unaltered flowing plasma, removing the need to extract the plasma from the body. This technology has provided the first opportunity to investigate whether microfluidic flow cell design can affect the capture of ctDNA in unaltered plasma. With inspiration from microfluidic mixer flow cells designed to capture circulating tumor cells and exosomes, we constructed four microfluidic mixer flow cells. Next, we investigated the effects of these flow cell designs and the flow rate on the rate of captured spiked-in BRAF T1799A (BRAFMut) ctDNA in unaltered flowing plasma using surface-immobilized dCas9. Once the optimal mass transfer rate of ctDNA, identified by the optimal ctDNA capture rate, was determined, we investigated whether the design of the microfluidic device, flow rate, flow time, and the number of spiked-in mutant DNA copies affected the rate of capture by the dCas9 capture system. We found that size modifications to the flow channel had no effect on the flow rate required to achieve the optimal capture rate of ctDNA. However, decreasing the size of the capture chamber decreased the flow rate required to achieve the optimal capture rate. Finally, we showed that, at the optimal capture rate, different microfluidic designs using different flow rates could capture DNA copies at a similar rate over time. In this study, the optimal capture rate of ctDNA in unaltered plasma was identified by adjusting the flow rate in each of the passive microfluidic mixer flow cells. However, further validation and optimization of the dCas9 capture system are required before it is ready to be used clinically.
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Affiliation(s)
- Bradley M Downs
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
| | - Tra-My Hoang
- Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, Maryland 21201, United States
| | - Leslie Cope
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
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21
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Salfati D, Huot M, Aparicio T, Lepage C, Taieb J, Bouché O, Boige V, Phelip JM, Dahan L, Bennouna J, Le Malicot K, Boussari O, Gornet JM. Carcinoembryonic antigen kinetics predict response to first-line treatment in metastatic colorectal cancer: Analysis from PRODIGE 9 trial. Dig Liver Dis 2023; 55:791-798. [PMID: 36725401 DOI: 10.1016/j.dld.2022.12.018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2022] [Revised: 11/20/2022] [Accepted: 12/26/2022] [Indexed: 02/03/2023]
Abstract
BACKGROUND To examine the relationship between carcinoembryonic antigen (CEA) kinetics and prognosis in metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the PRODIGE9 trial. METHODS Associations between monthly CEA measurements within 6 months since baseline and progression-free survival (PFS) were evaluated using a joint-latent class-mixed model. A validation set was used to test our prognosis model. Correlations between CEA trajectories (classes) and baseline characteristics were also investigated. RESULTS Three classes were identified. Class 1 had low baseline CEA with small variations. Class 2 had high baseline CEA with a rapid decrease reaching the same CEA level at 6 months as in class 1. Class 3 had high baseline CEA with a transient decrease followed by an increase to reach, at 6 months, the same CEA level as at baseline. Six-month PFS was significantly lower in class 3 than in classes 1 and 2 (57% vs. 91% and 93% respectively; p<0.01). Class 3 was significantly associated with ECOG 2 status, a high LDH level and non-resected primary tumor. DISCUSSION Variations in CEA kinetics correlate with prognosis in patients receiving first-line chemotherapy for mCRC. We propose here a user-friendly application to classify CEA trajectory.
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Affiliation(s)
- Delphine Salfati
- Assistance Publique - Hôpitaux de Paris, Hôpital Saint Louis, Université de Paris Cité, Paris, France
| | - Margaux Huot
- FFCD, EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France
| | - Thomas Aparicio
- Assistance Publique - Hôpitaux de Paris, Hôpital Saint Louis, Université de Paris Cité, Paris, France
| | - Come Lepage
- FFCD, EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France
| | - Julien Taieb
- Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Université de Paris, SIRIC CARPEM, Paris, France
| | - Olivier Bouché
- Department of Gastroenterology and Digestive Oncology, CHU Reims, Université de Reims Champagne-Ardenne (URCA), Reims, France
| | - Valérie Boige
- Department of Cancer Medicine, Gustave Roussy, Université Paris-Saclay Villejuif, France
| | - Jean-Marc Phelip
- Department of Gastroenterology and Digestive Oncology, University Hospital of Saint Etienne, Saint Etienne, France
| | - Laetitia Dahan
- Cancer Research Center of Marseille, CRCM, Inserm, CNRS, Paoli-Calmettes Institut, Aix-Marseille University, Marseille, France; La Timone Hospital, Marseille, France
| | | | - Karine Le Malicot
- FFCD, EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France
| | - Olayide Boussari
- FFCD, EPICAD INSERM LNC-UMR 1231, University of Burgundy and Franche Comté, Dijon, France
| | - Jean-Marc Gornet
- Assistance Publique - Hôpitaux de Paris, Hôpital Saint Louis, Université de Paris Cité, Paris, France.
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22
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On the use of spectroscopy, prediction machines and cybernetics for an affordable and proactive care approach for endometrial cancer. BIOMEDICAL ENGINEERING ADVANCES 2022. [DOI: 10.1016/j.bea.2022.100057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
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23
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Type XXII Collagen Complements Fibrillar Collagens in the Serological Assessment of Tumor Fibrosis and the Outcome in Pancreatic Cancer. Cells 2022; 11:cells11233763. [PMID: 36497023 PMCID: PMC9738409 DOI: 10.3390/cells11233763] [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] [Received: 09/30/2022] [Revised: 11/16/2022] [Accepted: 11/21/2022] [Indexed: 11/27/2022] Open
Abstract
Circulating fragments of type III collagen, measured by PRO-C3, has shown promising results as a tumor fibrosis biomarker. However, the fibrotic tumor microenvironment consists of many other collagens with diverse functions and unexplored biomarker potential. One example hereof is type XXII collagen (COL22). In this study, we investigated the biomarker potential of COL22 by measuring this in serum. An ELISA, named PRO-C22, was developed and measured in two serum cohorts consisting of patients with various solid tumors (n = 220) and healthy subjects (n = 33) (Cohort 1), and patients with pancreatic ductal adenocarcinoma (PDAC) (n = 34), and healthy subjects (n = 20) (Cohort 2). In Cohort 1, PRO-C22 was elevated in the serum from patients with solid tumors, compared to healthy subjects (p < 0.01 to p < 0.0001), and the diagnostic accuracy (AUROC) ranged from 0.87 to 0.98, p < 0.0001. In Cohort 2, the high levels of PRO-C22, in patients with PDAC, were predictive of a worse overall survival (HR = 4.52, 95% CI 1.90−10.7, p = 0.0006) and this remained significant after adjusting for PRO-C3 (HR = 4.27, 95% CI 1.24−10.4, p = 0.0013). In conclusion, PRO-C22 has diagnostic biomarker potential in various solid tumor types and prognostic biomarker potential in PDAC. Furthermore, PRO-C22 complemented PRO-C3 in predicting mortality, suggesting an additive prognostic value when quantifying different collagens.
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24
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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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25
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Dhanapala L, Joseph S, Jones AL, Moghaddam S, Lee N, Kremer RB, Rusling JF. Immunoarray Measurements of Parathyroid Hormone-Related Peptides Combined with Other Biomarkers to Diagnose Aggressive Prostate Cancer. Anal Chem 2022; 94:12788-12797. [PMID: 36074029 DOI: 10.1021/acs.analchem.2c02648] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Parathyroid hormone-related peptide (PTHrP) is related to bone metastasis and hypercalcemia in prostate and breast cancers and should be an excellent biomarker for aggressive forms of these cancers. Current clinical detection protocols for PTHrP are immunoradiometric assay and radioimmunoassay but are not sensitive enough to detect PTHrPs at early stages. We recently evaluated a prostate cancer biomarker panel, including serum monocyte differentiation antigen (CD-14), ETS-related gene protein, pigment epithelial-derived factor, and insulin-like growth factor-1, with promise for identifying aggressive prostate cancers. This panel predicted the need for patient biopsy better than PSA alone. In the present paper, we report an ultrasensitive microfluidic assay for PTHrPs and evaluate their diagnostic value and the value of including them with our prior biomarker panel to diagnose aggressive forms of prostate cancer. The immunoarray features screen-printed carbon sensor electrodes coated with 5 nm glutathione gold nanoparticles with capture antibodies attached. PTHrPs are bound to a secondary antibody attached to a polyhorseradish peroxidase label and delivered to the sensors to provide high sensitivity when activated by H2O2 and a mediator. We obtained an unprecedented 0.3 fg mL-1 limit of detection for PTHrP bioactive moieties PTHrP 1-173 and PTHrP 1-86. We also report the first study of PTHrPs in a large serum pool to identify aggressive malignancies. In assays of 130 human patient serum samples, PTHrP levels distinguished between aggressive and indolent prostate cancers with 83-91% clinical sensitivity and 78-96% specificity. Logistic regression identified the best predictive model as a combination of PTHrP 1-86 and vascular endothelial growth factor-D. PTHrP 1-173 alone also showed a high ability to differentiate aggressive and indolent cancers.
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Affiliation(s)
- Lasangi Dhanapala
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Sophie Joseph
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Abby L Jones
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States
| | - Shirin Moghaddam
- Department of Mathematics and Statistics (MACSI), University of Limerick, Limerick V94 T9PX, Ireland
| | - Norman Lee
- Department of Pharmacology and Physiology, George Washington University, 2300 I Street, NW, Washington, Washington, District of Columbia 20037, United States.,George Washington University Cancer Center, 800 22nd Street, NW, Washington, Washington, District of Columbia 20052, United States
| | - Richard B Kremer
- Department of Medicine, McGill University Health Centre, 1001 Decarie Blvd., Montreal QC H4A, Canada
| | - James F Rusling
- Department of Chemistry, University of Connecticut, Storrs, Connecticut 06269, United States.,Department of Surgery and Neag Cancer Center, UConn Health, Farmington, Connecticut 06232, United States.,School of Chemistry, National University of Ireland Galway, Galway H91 TK33, Ireland.,Institute of Materials Science, University of Connecticut, 97 N. Eagleville Road, Storrs, Connecticut 06269, United States
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26
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Mahmood T, Ved A, Siddiqui MH, Ahsan F, Shamim A, Ansari VA, Ahmad A, Kashyap MK. An in-Depth Analysis of Ovarian Cancer: Pathogenesis and Clinical Manifestation. Drug Res (Stuttg) 2022; 72:424-434. [PMID: 35760337 DOI: 10.1055/a-1867-4654] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
Abstract
Ovarian cancer is characterized by the establishment of tolerance, the recurrence of disease, as well as a poor prognosis. Gene signatures in ovarian cancer cells enable cancer medicine research, therapy, prevention, & management problematic. Notwithstanding advances in tumor puncture surgery, novel combinations regimens, and abdominal radiation, which can provide outstanding reaction times, the bulk of gynecological tumor patients suffer from side effects & relapse. As a consequence, more therapy alternatives for individuals with ovarian cancer must always be studied to minimize side effects and improve progression-free and total response rates. The development of cancer medications is presently undergoing a renaissance in the quest for descriptive and prognostic ovarian cancer biomarkers. Nevertheless, abnormalities in the BRCA2 or BRCA1 genes, a variety of hereditary predispositions, unexplained onset and progression, molecular tumor diversity, and illness staging can all compromise the responsiveness and accuracy of such indicators. As a result, current ovarian cancer treatments must be supplemented with broad-spectrum & customized targeted therapeutic approaches. The objective of this review is to highlight recent contributions to the knowledge of the interrelations between selected ovarian tumor markers, various perception signs, and biochemical and molecular signaling processes, as well as one's interpretation of much more targeted and effective treatment interventions.
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Affiliation(s)
- Tarique Mahmood
- Department of Pharmacy, Integral University, Dasauli, Lucknow, India
| | - Akash Ved
- Department of Pharmacy, Goel Institute of Pharmaceutical Sciences, Lucknow, India
| | | | - Farogh Ahsan
- Department of Pharmacy, Integral University, Dasauli, Lucknow, India
| | - Arshiya Shamim
- Department of Pharmacy, Integral University, Dasauli, Lucknow, India
| | | | - Afroz Ahmad
- Department of Pharmacy, Integral University, Dasauli, Lucknow, India
| | - Monu Kumar Kashyap
- Department of Pharmacy, Goel Institute of Pharmaceutical Sciences, Lucknow, India
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27
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Zhang Y, Zhao Y, Cole T, Zheng J, Bayinqiaoge, Guo J, Tang SY. Microfluidic flow cytometry for blood-based biomarker analysis. Analyst 2022; 147:2895-2917. [PMID: 35611964 DOI: 10.1039/d2an00283c] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Flow cytometry has proven its capability for rapid and quantitative analysis of individual cells and the separation of targeted biological samples from others. The emerging microfluidics technology makes it possible to develop portable microfluidic diagnostic devices for point-of-care testing (POCT) applications. Microfluidic flow cytometry (MFCM), where flow cytometry and microfluidics are combined to achieve similar or even superior functionalities on microfluidic chips, provides a powerful single-cell characterisation and sorting tool for various biological samples. In recent years, researchers have made great progress in the development of the MFCM including focusing, detecting, and sorting subsystems, and its unique capabilities have been demonstrated in various biological applications. Moreover, liquid biopsy using blood can provide various physiological and pathological information. Thus, biomarkers from blood are regarded as meaningful circulating transporters of signal molecules or particles and have great potential to be used as non (or minimally)-invasive diagnostic tools. In this review, we summarise the recent progress of the key subsystems for MFCM and its achievements in blood-based biomarker analysis. Finally, foresight is offered to highlight the research challenges faced by MFCM in expanding into blood-based POCT applications, potentially yielding commercialisation opportunities.
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Affiliation(s)
- Yuxin Zhang
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
| | - Ying Zhao
- National Chengdu Centre of Safety Evaluation of Drugs, West China Hospital of Sichuan University, Chengdu, China
| | - Tim Cole
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
| | - Jiahao Zheng
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
| | - Bayinqiaoge
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
| | - Jinhong Guo
- The M.O.E. Key Laboratory of Laboratory Medical Diagnostics, The College of Laboratory Medicine, Chongqing Medical University, #1 Yixueyuan Road, Yuzhong District, Chongqing, 400016, China.
| | - Shi-Yang Tang
- Department of Electronic, Electrical and Systems Engineering, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
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28
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Downs BM, Sukumar S. Capturing ctDNA from Unaltered Stationary and Flowing Plasma with dCas9. ACS APPLIED MATERIALS & INTERFACES 2022; 14:24113-24121. [PMID: 35603357 DOI: 10.1021/acsami.2c03186] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Many studies have established that blood-based liquid biopsies can be used to detect cancer in its early stages. However, the limiting factor for early cancer detection is the volume of blood required to capture the small amount of circulating tumor DNA (ctDNA). An apheresis machine is a device that can draw whole blood, separate the blood components, and infuse the blood components back into the individual. This device provides the opportunity to screen large volumes of plasma without extracting it from the body. However, current DNA capture technologies require the plasma to be altered before the ctDNA can be captured. Our goal was to develop the first technology that can capture ctDNA from flowing unaltered plasma. To simulate cancer patient plasma, we spiked BRAF T1799A (BRAFMut) DNA into plasma from healthy individuals. We used catalytically dead Cas9 (dCas9), guide RNA, and allele-specific quantitative polymerase chain reaction (qPCR) to capture and measure the number of captured BRAFMut DNA copies. We found that dCas9 captured BRAFMut alleles with equal efficiency at room temperature (25 °C) and body temperature (37 °C). Next, we showed that, in stationary unaltered plasma, dCas9 was as efficient in capturing BRAFMut as a commercial cell-free DNA (cfDNA) capture kit. However, in contrast to the cfDNA capture kit, dCas9 enriched BRAFMut by 1.8-3.3-fold. We then characterized the dCas9 capture system in laminar and turbulent flowing plasma. We showed that the capture rate using turbulent flow was greater than that in laminar flow and stationary plasma. With turbulent flow, the number of captured BRAFMut copies doubles with time (slope = -1.035 Ct) and is highly linear (R2 = 0.874). While we showed that the dCas9 capture system can capture ctDNA from unaltered flowing plasma, further optimization and validation of this technology is required before its clinical utility can be determined.
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Affiliation(s)
- Bradley M Downs
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
| | - Saraswati Sukumar
- Department of Oncology, The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, United States
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29
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Tang Q, Liu H, Qi J, Yan X, Mustafa A, Xi Y, Li J, Bai L, Liang L, Han C, Wang J. Mass spectrometry-based metabolic profiling for identification of biomarkers in serum related to the change of laying ducks in different physiological periods. ITALIAN JOURNAL OF ANIMAL SCIENCE 2022. [DOI: 10.1080/1828051x.2022.2063768] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Qian Tang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Hehe Liu
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Jingjing Qi
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Xiping Yan
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Ahsan Mustafa
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Yang Xi
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Junpeng Li
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Lili Bai
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Li Liang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Chunchun Han
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
| | - Jiwen Wang
- College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China
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30
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Khan MZI, Tam MSY, Azam Z, Law HKW. Proteomic profiling of metabolic proteins as potential biomarkers of radioresponsiveness for colorectal cancer. J Proteomics 2022; 262:104600. [DOI: 10.1016/j.jprot.2022.104600] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Revised: 04/25/2022] [Accepted: 05/01/2022] [Indexed: 12/24/2022]
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31
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Singh A, Prakash V, Gupta N, Kumar A, Kant R, Kumar D. Serum Metabolic Disturbances in Lung Cancer Investigated through an Elaborative NMR-Based Serum Metabolomics Approach. ACS OMEGA 2022; 7:5510-5520. [PMID: 35187366 PMCID: PMC8851899 DOI: 10.1021/acsomega.1c06941] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 01/18/2022] [Indexed: 06/01/2023]
Abstract
Detection of metabolic disturbances in lung cancer (LC) has the potential to aid early diagnosis/prognosis and hence improve disease management strategies through reliable grading, staging, and determination of neoadjuvant status in LC. However, a majority of previous metabolomics studies compare the normalized spectral features which not only provide ambiguous information but further limit the clinical translation of this information. Various such issues can be resolved by performing the concentration profiling of various metabolites with respect to formate as an internal reference using commercial software Chenomx. Continuing our efforts in this direction, the serum metabolic profiles were measured on 39 LC patients and 42 normal controls (NCs, comparable in age/sex) using high-field 800 MHz NMR spectroscopy and compared using multivariate statistical analysis tools to identify metabolic disturbances and metabolites of diagnostic potential. Partial least-squares discriminant analysis (PLS-DA) model revealed a distinct separation between LC and NC groups and resulted in excellent discriminatory ability with the area under the receiver-operating characteristic (AUROC) = 0.97 [95% CI = 0.89-1.00]. The metabolic features contributing to the differentiation of LC from NC samples were identified first using variable importance in projection (VIP) score analysis and then checked for their statistical significance (with p-value < 0.05) and diagnostic potential using the ROC curve analysis. The analysis revealed relevant metabolic disturbances associated with LC. Among various circulatory metabolites, six metabolites, including histidine, glutamine, glycine, threonine, alanine, and valine, were found to be of apposite diagnostic potential for clinical implications. These metabolic alterations indicated altered glucose metabolism, aberrant fatty acid synthesis, and augmented utilization of various amino acids including active glutaminolysis in LC.
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Affiliation(s)
- Anjana Singh
- All
India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand 249201, India
- Pulmonary
& Critical Care Medicine, King George’s
Medical University, Lucknow, Uttar Pradesh 226003, India
| | - Ved Prakash
- Pulmonary
& Critical Care Medicine, King George’s
Medical University, Lucknow, Uttar Pradesh 226003, India
| | - Nikhil Gupta
- Centre
of Biomedical Research (CBMR), SGPGIMS, Lucknow, Uttar Pradesh 226014, India
- Department
of Chemistry, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Ashish Kumar
- Department
of Chemistry, Banaras Hindu University, Varanasi, Uttar Pradesh 221005, India
| | - Ravi Kant
- All
India Institute of Medical Sciences (AIIMS), Rishikesh, Uttarakhand 249201, India
| | - Dinesh Kumar
- Centre
of Biomedical Research (CBMR), SGPGIMS, Lucknow, Uttar Pradesh 226014, India
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32
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Kalita-de Croft P, Joshi V, Saunus JM, Lakhani SR. Emerging Biomarkers for Diagnosis, Prevention and Treatment of Brain Metastases-From Biology to Clinical Utility. Diseases 2022; 10:11. [PMID: 35225863 PMCID: PMC8884016 DOI: 10.3390/diseases10010011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 01/18/2022] [Accepted: 01/27/2022] [Indexed: 11/17/2022] Open
Abstract
Primary malignancies of the lung, skin (melanoma), and breast have higher propensity for metastatic spread to the brain. Advances in molecular tumour profiling have aided the development of targeted therapies, stereotactic radiotherapy, and immunotherapy, which have led to some improvement in patient outcomes; however, the overall prognosis remains poor. Continued research to identify new prognostic and predictive biomarkers is necessary to further impact patient outcomes, as this will enable better risk stratification at the point of primary cancer diagnosis, earlier detection of metastatic deposits (for example, through surveillance), and more effective systemic treatments. Brain metastases exhibit considerable inter- and intratumoural heterogeneity-apart from distinct histology, treatment history and other clinical factors, the metastatic brain tumour microenvironment is incredibly variable both in terms of subclonal diversity and cellular composition. This review discusses emerging biomarkers; specifically, the biological context and potential clinical utility of tumour tissue biomarkers, circulating tumour cells, extracellular vesicles, and circulating tumour DNA.
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Affiliation(s)
- Priyakshi Kalita-de Croft
- UQ Centre for Clinical Research, The University of Queensland Faculty of Medicine, Herston, QLD 4029, Australia; (V.J.); (J.M.S.)
| | - Vaibhavi Joshi
- UQ Centre for Clinical Research, The University of Queensland Faculty of Medicine, Herston, QLD 4029, Australia; (V.J.); (J.M.S.)
| | - Jodi M. Saunus
- UQ Centre for Clinical Research, The University of Queensland Faculty of Medicine, Herston, QLD 4029, Australia; (V.J.); (J.M.S.)
| | - Sunil R. Lakhani
- UQ Centre for Clinical Research, The University of Queensland Faculty of Medicine, Herston, QLD 4029, Australia; (V.J.); (J.M.S.)
- Pathology Queensland, The Royal Brisbane and Women’s Hospital Herston, Herston, QLD 4029, Australia
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33
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Akbar S, Majeed MI, Nawaz H, Rashid N, Tariq A, Hameed W, Shakeel S, Dastgir G, Bari RZA, Iqbal M, Nawaz A, Akram M. Surface-Enhanced Raman Spectroscopic (SERS) Characterization of Low Molecular Weight Fraction of the Serum of Breast Cancer Patients with Principal Component Analysis (PCA) and Partial Least Square-Discriminant Analysis (PLS-DA). ANAL LETT 2021. [DOI: 10.1080/00032719.2021.2017948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Saba Akbar
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | | | - Haq Nawaz
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Nosheen Rashid
- Department of Chemistry, University of Education, Faisalabad, Pakistan
| | - Ayesha Tariq
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Wajeeha Hameed
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Samra Shakeel
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Ghulam Dastgir
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Rana Zaki Abdul Bari
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Maham Iqbal
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Amna Nawaz
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
| | - Maria Akram
- Department of Chemistry, University of Agriculture Faisalabad, Faisalabad, Pakistan
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34
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Sadeghi H, Kamal A, Ahmadi M, Najafi H, Sharifi Zarchi A, Haddad P, Shayestehpour B, Kamkar L, Salamati M, Geranpayeh L, Lashkari M, Totonchi M. A novel panel of blood-based microRNAs capable of discrimination between benign breast disease and breast cancer at early stages. RNA Biol 2021; 18:747-756. [PMID: 34793290 DOI: 10.1080/15476286.2021.1989218] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Breast cancer (BC) as a leading cause of cancer death among women, exhibits a wide range of genetic heterogeneity in affected individuals. Satisfactory management of BC depends on early diagnosis and proper monitoring of patients' response to therapy. In this study, we aimed to assess the relation between the expression patterns of blood-based microRNAs (miRNAs) with demographic characteristics of the patients with BC in an attempt to find novel diagnostic markers for BC with acceptable precision in clinical applications. To this end, we performed comprehensive statistical analysis of the data of the Cancer Genome Atlas (TCGA) database and the blood miRNome dataset (GSE31309). As a result, 21 miRNAs were selected for experimental verification by quantitative RT-PCR on blood samples of 70 BC patients and 60 normal individuals (without any lesions or benign breast diseases). Statistical one-way ANOVA revealed no significant difference in the blood levels of the selected miRNAs in BC patients compared to any lesions or benign breast diseases. However, the multi-marker panel consisting of hsa-miR-106b-5p, -126-3p, -140-3p, -193a-5p, and -10b-5p could detect early-stages of BC with 0.79 sensitivity, 0.86 specificity and 0.82 accuracy. Furthermore, this multi-marker panel showed the potential of detecting benign breast diseases from BC patients with 0.67 sensitivity, 0.80 specificity, and 0.74 accuracy. In conclusion, these data indicate that the present panel might be considered an asset in detecting benign breast disease and BC.
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Affiliation(s)
- Hanieh Sadeghi
- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Acecr, Tehran, Iran
| | - Aryan Kamal
- Department of Clinical Bioinformatics, Saarland University, Saarbrücken, Germany
| | - Marzieh Ahmadi
- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Acecr, Tehran, Iran
| | - Hadi Najafi
- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Acecr, Tehran, Iran
| | - Ali Sharifi Zarchi
- Department of Computer Engineering, Sharif University of Technology, Tehran, Iran
| | - Peyman Haddad
- Radiation Oncology Research Center, Iran Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bahareh Shayestehpour
- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Acecr, Tehran, Iran
| | - Leila Kamkar
- Department of Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran
| | - Masoumeh Salamati
- Department of Reproductive Imaging, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Acecr, Tehran, Iran
| | - Loabat Geranpayeh
- Department of Surgery, Sina Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Marzieh Lashkari
- Radiation Oncology Research Center, Iran Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Totonchi
- Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, Acecr, Tehran, Iran
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Wang X, Ye Y, Huang Z, Seeberger PH, Hu J, Yin J. In vivo dual fluorescence imaging of mucin 1 and its glycoform in tumor cells. NANOSCALE 2021; 13:15067-15073. [PMID: 34533554 DOI: 10.1039/d1nr02821a] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Abstract
The most efficient approach for cancer identification and monitoring is the detection of cancer-associated protein biomarkers but an accurate diagnosis requires multiple analyses. Glycosylation profiling can provide important biological information since different glycoforms are involved in malignant transformation. Here, a near-infrared (NIR) light activated fluorescence resonance energy transfer (FRET) strategy for the efficient and reliable simultaneous dual imaging of the mucin 1 (MUC1) protein backbone and MUC1-specific sialic acid (Sia) is reported. MUC1, an important tumor biomarker, is overexpressed and under-glycosylated in most tumor cells. Two aptamer-functionalized nanoprobes, Cy5-labeled Sia aptamer-functionalized gold nanostars (Sia-GNSs) and MUC1 aptamer-functionalized quantum dots (MUC1-QDs), were successfully constructed with high specificity and biocompatibility. Upon excitation with NIR light, Sia-GNSs endothermically released the Cy5-labeled Sia aptamer that specifically binds to Sia. The Cy5 fluorescence can be observed due to the FRET effect when the Cy5-labeled Sia aptamer and MUC1-QDs bind to the same MUC1 molecule. Dual imaging and relative quantification of MUC1 and its sialylation were achieved in vitro, in vivo and in clinical tissue samples. This efficient platform allows for the simultaneous detection of protein biomarkers and their glycosylation pattern, with significant potential for clinical cancer diagnostics.
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Affiliation(s)
- Xiaoli Wang
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.
| | - Yufei Ye
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.
| | - Zhaohui Huang
- Wuxi School of Medicine, Jiangnan University, Wuxi 214122, PR China.
| | - Peter H Seeberger
- Department of Biomolecular Systems, Max-Plank Institute of Colloids and Interfaces, Potsdam 14476, Germany
| | - Jing Hu
- Wuxi School of Medicine, Jiangnan University, Wuxi 214122, PR China.
| | - Jian Yin
- Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi 214122, PR China.
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Sefrioui D, Beaussire L, Gillibert A, Blanchard F, Toure E, Bazille C, Perdrix A, Ziegler F, Gangloff A, Hassine M, Elie C, Bignon AL, Parzy A, Gomez P, Thill C, Clatot F, Sabourin JC, Frebourg T, Benichou J, Bouhier-Leporrier K, Gallais MP, Sarafan-Vasseur N, Michel P, Di Fiore F. CEA, CA19-9, circulating DNA and circulating tumour cell kinetics in patients treated for metastatic colorectal cancer (mCRC). Br J Cancer 2021; 125:725-733. [PMID: 34112948 PMCID: PMC8405627 DOI: 10.1038/s41416-021-01431-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 04/17/2021] [Accepted: 04/28/2021] [Indexed: 02/03/2023] Open
Abstract
BACKGROUND We previously reported that CEA kinetics are a marker of progressive disease (PD) in metastatic colorectal cancer (mCRC). This study was specifically designed to confirm CEA kinetics for predicting PD and to evaluate CA19-9, cell-free DNA (cfDNA), circulating tumour DNA (ctDNA) and circulating tumour cell (CTC) kinetics. METHODS Patients starting a chemotherapy (CT) with pre-treatment CEA > 5 ng/mL and/or CA19.9 > 30 UI/mL were prospectively included. Samples were collected from baseline to cycle 4 for CEA and CA19-9 and at baseline and the sixth week for other markers. CEA kinetics were calculated from the first to the third or fourth CT cycle. RESULTS A total of 192 mCRC patients were included. CEA kinetics based on the previously identified >0.05 threshold was significantly associated with PD (p < 0.0001). By dichotomising by the median value, cfDNA, ctDNA and CA19-9 were associated with PD, PFS and OS in multivariate analysis. A circulating scoring system (CSS) combining CEA kinetics and baseline CA19-9 and cfDNA values classified patients based on high (n = 58) and low risk (n = 113) of PD and was independently associated with PD (ORa = 4.6, p < 0.0001), PFS (HRa = 2.07, p < 0.0001) and OS (HRa = 2.55, p < 0.0001). CONCLUSIONS CEA kinetics alone or combined with baseline CA19-9 and cfDNA are clinically relevant for predicting outcomes in mCRC. TRIAL REGISTRATION NUMBER NCT01212510.
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Affiliation(s)
- David Sefrioui
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine and Department of Hepatogastroenterology, Rouen, France
| | - Ludivine Beaussire
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France
| | - André Gillibert
- grid.41724.34Department of Biostatistics, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
| | - France Blanchard
- grid.41724.34Department of Pathology, Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France
| | - Emmanuel Toure
- grid.41724.34Department of Pathology, Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France
| | - Céline Bazille
- grid.411149.80000 0004 0472 0160Department of Pathology, Caen University Hospital, Caen, France
| | - Anne Perdrix
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine and Department of Biopathology, Henri Becquerel Centre, Rouen, France
| | - Frédéric Ziegler
- grid.7429.80000000121866389Normandie Univ, UNIROUEN, INSERM U1073, Rouen University Hospital and General Biochemistry Laboratory, Institute of Clinical Biology, Rouen, France
| | - Alice Gangloff
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine and Department of Hepatogastroenterology, Rouen, France
| | - Mélanie Hassine
- Department of Hepatogastroenterology, Elbeuf Hospital, Elbeuf, France
| | - Caroline Elie
- Department of Hepatogastroenterology, Elbeuf Hospital, Elbeuf, France
| | - Anne-Laure Bignon
- grid.411149.80000 0004 0472 0160Department of Hepatogastroenterology, Caen University Hospital, Caen, France
| | - Aurélie Parzy
- Department of Hepatogastroenterology, Francois Baclesse Centre, Caen, France
| | - Philippe Gomez
- Department of Medical Oncology, Frédéric Joliot Centre, Rouen, France
| | - Caroline Thill
- grid.41724.34Department of Biostatistics, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Florian Clatot
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine and Department of Medical Oncology, Henri Becquerel Centre, Rouen, France
| | - Jean-Christophe Sabourin
- grid.41724.34Department of Pathology, Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France
| | - Thierry Frebourg
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine and Department of Genetics, Rouen, France
| | - Jacques Benichou
- grid.41724.34Department of Biostatistics, Normandie Univ, UNIROUEN, Rouen University Hospital, Rouen, France
| | - Karine Bouhier-Leporrier
- grid.411149.80000 0004 0472 0160Department of Hepatogastroenterology, Caen University Hospital, Caen, France
| | | | - Nasrin Sarafan-Vasseur
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France
| | - Pierre Michel
- grid.41724.34Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine and Department of Hepatogastroenterology, Rouen, France
| | - Frédéric Di Fiore
- grid.41724.34Department of Hepatogastroenterology and Department of Medical Oncology, Henri Becquerel Centre, Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Normandy Centre for Genomic and Personalized Medicine, Rouen, France
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Sourani A, Saghaei S, Sabouri M, Soleimani M, Dehghani L. A systematic review of extracellular vesicles as non-invasive biomarkers in glioma diagnosis, prognosis, and treatment response monitoring. Mol Biol Rep 2021; 48:6971-6985. [PMID: 34460059 DOI: 10.1007/s11033-021-06687-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Accepted: 08/24/2021] [Indexed: 12/23/2022]
Abstract
The present systematic review was done to investigate the possible application of Extracellular vesicles (EVs) in the diagnosis, prognosis, and treatment response monitoring of gliomas using available literature to wrap up the final applicable conclusion in this regard. we searched PubMed/MEDLINE, Scopus, and ISI Web of Science databases. Authors evaluated the quality of the included studies by the QUADAS-2 tool. In total, 2037 published datasets were retrieved through systematic search. Upon screening for eligibility, 35 datasets were determined as eligible. Exosome was the EV-subtype described in the majority of studies, and most datasets used serum as the primary EVs isolation source. EVs isolation was primarily conducted by ultracentrifugation. 31 datasets reported that EVs hold considerable potential for being used in diagnostics, with the majority reporting different types of miRNAs as biomarkers. Besides, 8 datasets reported that EVs could be a potential source of prognostic biomarkers. And finally, 3 datasets reported that EVs might be a reliable strategy for monitoring therapy response in glioma patients. According to the findings of the current systematic review, it seems that miR-301, miR-21, and HOTAIR had the highest diagnostic accuracy. However, heterogeneous and limited evidence regarding prognosis and treatment response monitoring precludes us from drawing a practical conclusion regarding EVs.
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Affiliation(s)
- Arman Sourani
- Department of Neurosurgery, Isfahan University of Medical Sciences, Isfahan, Iran.
| | - Saeid Saghaei
- Department of Neurosurgery, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masih Sabouri
- Department of Neurosurgery, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Masoud Soleimani
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Leila Dehghani
- Neurosciences Research Center, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
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Zhou X, Liu C, Yin Y, Zhang C, Zou X, Xia T, Geng X, Liu P, Cheng W, Zhu W. Diagnostic value of oncofetal miRNAs in cancers: A comprehensive analysis of circulating miRNAs in pan-cancers and UCB. Cancer Biomark 2021; 32:19-36. [PMID: 34092608 DOI: 10.3233/cbm-203085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Circulating miRNAs are promising biomarkers for detection of various cancers. As a "developmental" disorder, cancer showed great similarities with embryos. OBJECTIVE A comprehensive analysis of circulating miRNAs in umbilical cord blood (UCB) and pan-cancers was conducted to identify circulating miRNAs with potential for cancer detection. METHODS A total of 3831 cancer samples (2050 serum samples from 15 types of cancers and 1781 plasma samples from 13 types of cancers) and 248 UCB samples (120 serum and 128 plasma samples) with corresponding NCs from Chinese populations were analyzed via consistent experiment workflow with Exiqon panel followed by multiple-stage validation with qRT-PCR. RESULTS Thirty-four serum and 32 plasma miRNAs were dysregulated in at least one type of cancer. Eighteen serum and 16 plasma miRNAs were related with embryos. Among them, 9 serum and 8 plasma miRNAs with consistent expression patterns between pan-cancers and UCB were identified as circulating oncofetal miRNAs. Retrospective analysis confirmed the diagnostic ability of circulating oncofetal miRNAs for specific cancers. And the oncofetal miRNAs were mainly up-regulated in tissues of pan-cancers. CONCLUSIONS Our study might serve as bases for the potential application of the non-invasive biomarkers in the future clinical.
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Affiliation(s)
- Xin Zhou
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Cheng Liu
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Yin Yin
- Department of Gynecology and Obstetrics, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Cheng Zhang
- Women&Children Central Laboratory, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xuan Zou
- First Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Tiansong Xia
- Jiangsu Breast Disease Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Xiangnan Geng
- Department of Clinical Engineering, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Ping Liu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Wenfang Cheng
- Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Wei Zhu
- Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
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Yusifov A, Chhatre VE, Koplin EK, Wilson CE, Schmitt EE, Woulfe KC, Bruns DR. Transcriptomic analysis of cardiac gene expression across the life course in male and female mice. Physiol Rep 2021; 9:e14940. [PMID: 34245129 PMCID: PMC8271347 DOI: 10.14814/phy2.14940] [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: 05/06/2021] [Revised: 05/22/2021] [Accepted: 05/29/2021] [Indexed: 12/13/2022] Open
Abstract
Risk for heart disease increases with advanced age and differs between sexes, with females generally protected from heart disease until menopause. Despite these epidemiological observations, the molecular mechanisms that underlie sex‐specific differences in cardiac function have not been fully described. We used high throughput transcriptomics in juvenile (5 weeks), adult (4–6 months), and aged (18 months) male and female mice to understand how cardiac gene expression changes across the life course and by sex. While male gene expression profiles differed between juvenile‐adult and juvenile‐aged (254 and 518 genes, respectively), we found no significant differences in adult‐aged gene expression. Females had distinct gene expression changes across the life course with 1835 genes in juvenile‐adult and 1328 in adult‐aged. Analysis of differentially expressed genes (DEGs) suggests that juvenile to adulthood genes were clustered in cell cycle and development‐related pathways in contrast to adulthood‐aged which were characterized by immune‐and inflammation‐related pathways. Analysis of sex differences within each age suggests that juvenile and aged cardiac transcriptomes are different between males and females, with significantly fewer DEGs identified in adult males and females. Interestingly, the male–female differences in early age were distinct from those in advanced age. These findings are in contrast to expected sex differences historically attributed to estrogen and could not be explained by estrogen‐direct mechanisms alone as evidenced by juvenile sexual immaturity and reproductive incompetence in the aged mice. Together, distinct trajectories in cardiac transcriptomic profiles highlight fundamental sex differences across the life course and demonstrate the need for the consideration of age and sex as biological variables in heart disease.
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Affiliation(s)
- Aykhan Yusifov
- Kinesiology and Health, University of Wyoming, Laramie, WY, USA
| | | | - Eva K Koplin
- Kinesiology and Health, University of Wyoming, Laramie, WY, USA
| | - Cortney E Wilson
- Division of Cardiology, University of Colorado-Denver, Aurora, CO, USA
| | - Emily E Schmitt
- Kinesiology and Health, University of Wyoming, Laramie, WY, USA
| | - Kathleen C Woulfe
- Division of Cardiology, University of Colorado-Denver, Aurora, CO, USA.,Division of Geriatric Medicine, University of Colorado-Denver, Aurora, CO, USA
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Kochan K, Bedolla DE, Perez-Guaita D, Adegoke JA, Chakkumpulakkal Puthan Veettil T, Martin M, Roy S, Pebotuwa S, Heraud P, Wood BR. Infrared Spectroscopy of Blood. APPLIED SPECTROSCOPY 2021; 75:611-646. [PMID: 33331179 DOI: 10.1177/0003702820985856] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
The magnitude of infectious diseases in the twenty-first century created an urgent need for point-of-care diagnostics. Critical shortages in reagents and testing kits have had a large impact on the ability to test patients with a suspected parasitic, bacteria, fungal, and viral infections. New point-of-care tests need to be highly sensitive, specific, and easy to use and provide results in rapid time. Infrared spectroscopy, coupled to multivariate and machine learning algorithms, has the potential to meet this unmet demand requiring minimal sample preparation to detect both pathogenic infectious agents and chronic disease markers in blood. This focal point article will highlight the application of Fourier transform infrared spectroscopy to detect disease markers in blood focusing principally on parasites, bacteria, viruses, cancer markers, and important analytes indicative of disease. Methodologies and state-of-the-art approaches will be reported and potential confounding variables in blood analysis identified. The article provides an up to date review of the literature on blood diagnosis using infrared spectroscopy highlighting the recent advances in this burgeoning field.
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Affiliation(s)
- Kamila Kochan
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | - Diana E Bedolla
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | - David Perez-Guaita
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | - John A Adegoke
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | | | - Miguela Martin
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | - Supti Roy
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | - Savithri Pebotuwa
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | - Philip Heraud
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
| | - Bayden R Wood
- 2541Monash University - Centre for Biospectroscopy, Clayton, Victoria, Australia
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Integration of machine learning and genome-scale metabolic modeling identifies multi-omics biomarkers for radiation resistance. Nat Commun 2021; 12:2700. [PMID: 33976213 PMCID: PMC8113601 DOI: 10.1038/s41467-021-22989-1] [Citation(s) in RCA: 109] [Impact Index Per Article: 27.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Accepted: 04/09/2021] [Indexed: 02/07/2023] Open
Abstract
Resistance to ionizing radiation, a first-line therapy for many cancers, is a major clinical challenge. Personalized prediction of tumor radiosensitivity is not currently implemented clinically due to insufficient accuracy of existing machine learning classifiers. Despite the acknowledged role of tumor metabolism in radiation response, metabolomics data is rarely collected in large multi-omics initiatives such as The Cancer Genome Atlas (TCGA) and consequently omitted from algorithm development. In this study, we circumvent the paucity of personalized metabolomics information by characterizing 915 TCGA patient tumors with genome-scale metabolic Flux Balance Analysis models generated from transcriptomic and genomic datasets. Metabolic biomarkers differentiating radiation-sensitive and -resistant tumors are predicted and experimentally validated, enabling integration of metabolic features with other multi-omics datasets into ensemble-based machine learning classifiers for radiation response. These multi-omics classifiers show improved classification accuracy, identify clinical patient subgroups, and demonstrate the utility of personalized blood-based metabolic biomarkers for radiation sensitivity. The integration of machine learning with genome-scale metabolic modeling represents a significant methodological advancement for identifying prognostic metabolite biomarkers and predicting radiosensitivity for individual patients.
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Ryu J, Thomas SN. Quantitative Mass Spectrometry-Based Proteomics for Biomarker Development in Ovarian Cancer. Molecules 2021; 26:molecules26092674. [PMID: 34063568 PMCID: PMC8125593 DOI: 10.3390/molecules26092674] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 04/29/2021] [Accepted: 05/01/2021] [Indexed: 12/11/2022] Open
Abstract
Ovarian cancer is the most lethal gynecologic malignancy among women. Approximately 70–80% of patients with advanced ovarian cancer experience relapse within five years and develop platinum-resistance. The short life expectancy of patients with platinum-resistant or platinum-refractory disease underscores the need to develop new and more effective treatment strategies. Early detection is a critical step in mitigating the risk of disease progression from early to an advanced stage disease, and protein biomarkers have an integral role in this process. The best biological diagnostic tool for ovarian cancer will likely be a combination of biomarkers. Targeted proteomics methods, including mass spectrometry-based approaches, have emerged as robust methods that can address the chasm between initial biomarker discovery and the successful verification and validation of these biomarkers enabling their clinical translation due to the robust sensitivity, specificity, and reproducibility of these versatile methods. In this review, we provide background information on the fundamental principles of biomarkers and the need for improved treatment strategies in ovarian cancer. We also provide insight into the ways in which mass spectrometry-based targeted proteomics approaches can provide greatly needed solutions to many of the challenges related to ovarian cancer biomarker development.
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Tan Z, Zou Y, Zhu M, Luo Z, Wu T, Zheng C, Xie A, Wang H, Fang S, Liu S, Li Y, Lu Z. Carnitine palmitoyl transferase 1A is a novel diagnostic and predictive biomarker for breast cancer. BMC Cancer 2021; 21:409. [PMID: 33858374 PMCID: PMC8048260 DOI: 10.1186/s12885-021-08134-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 12/16/2020] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Carnitine palmitoyl transferase 1A (CPT1A), the key regulator of fatty acid oxidation, contributes to tumor metastasis and therapeutic resistance. We aimed to identify its clinical significance as a biomarker for the diagnosis and prediction of breast cancer. METHODS Western blot, ELISA and in silico analysis were used to confirm CPT1A levels in breast cancer cell lines, cell culture medium and breast cancer tissues. Four hundred thirty breast cancer patients, 200 patients with benign breast disease, and 400 healthy controls were enrolled and randomly divided into a training set and a test set with a 7:3 ratio. Training set was used to build diagnostic models and 10-fold cross validation was used to demonstrate the performance of the models. Then test set was aimed to validate the effectiveness of the diagnostic models. ELISA was conducted to detect individual serum CPT1A levels. Receiver operating characteristic (ROC) curves were generated, and binary logistic regression analyses were performed to evaluate the effectiveness of CPT1A as a biomarker in breast cancer diagnosis. CPT1A levels between post-operative and pre-operative samples were also compared. RESULTS CPT1A was overexpressed in breast cancer tissues, cell lines and cell culture medium. Serum CPT1A levels were higher in breast cancer patients than in controls and were significantly associated with metastasis, TNM stage, histological grading and molecular subtype. CPT1A levels were decreased in post-operative samples compared with paired pre-operative samples. Moreover, CPT1A exhibited a higher efficacy in differentiating breast cancer patients from healthy controls (training set: area under the curve, AUC, 0.892, 95% CI, 0.872-0.920; test set, AUC, 0.904, 95% CI, 0.869-0.939) than did CA15-3, CEA, or CA125. CONCLUSION CPT1A is overexpressed in breast cancer and can be secreted out of breast cancer cell. Serum CPT1A is positively associated with breast cancer progression and could serve as an indicator for disease monitoring. Serum CPT1A displayed a remarkably high diagnostic efficiency for breast cancer and could be a novel biomarker for the diagnosis of breast cancer.
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Affiliation(s)
- Zheqiong Tan
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China.
| | - Yaru Zou
- Department of Clinical Laboratory, Wusong Central Hospital, Baoshan District, Shanghai, 200940, China
| | - Man Zhu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Zhenzhao Luo
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Tangwei Wu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Chao Zheng
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Aqing Xie
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Hui Wang
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Shiqiang Fang
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Shuiyi Liu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
- Cancer Research Institute of Wuhan, Wuhan, 430014, Hubei, China
- Department of Central Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China
| | - Yong Li
- Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA
- Department of Medicine, Section of Epidemiology and Population Sciences, Baylor College of Medicine, Houston, TX, 77030, USA
| | - Zhongxin Lu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430014, Hubei, China.
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Highly Sensitive and Cost-Effective Portable Sensor for Early Gastric Carcinoma Diagnosis. SENSORS 2021; 21:s21082639. [PMID: 33918707 PMCID: PMC8069728 DOI: 10.3390/s21082639] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Revised: 03/23/2021] [Accepted: 03/25/2021] [Indexed: 11/17/2022]
Abstract
Facile and efficient early detection of cancer is a major challenge in healthcare. Herein we developed a novel sensor made from a polycarbonate (PC) membrane with nanopores, followed by sequence-specific Oligo RNA modification for early gastric carcinoma diagnosis. In this design, the gastric cancer antigen CA72-4 is specifically conjugated to the Oligo RNA, thereby inhibiting the electrical current through the PC membrane in a concentration-dependent manner. The device can determine the concentration of cancer antigen CA72-4 in the range from 4 to 14 U/mL, possessing a sensitivity of 7.029 µAU-1mLcm-2 with a linear regression (R2) of 0.965 and a lower detection limit of 4 U/mL. This device has integrated advantages including high specificity and sensitivity and being simple, portable, and cost effective, which collectively enables a giant leap for cancer screening technologies towards clinical use. This is the first report to use RNA aptamers to detect CA72-4 for gastric carcinoma diagnosis.
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Hong CQ, Weng XF, Huang XC, Chu LY, Wei LF, Lin YW, Chen LY, Liu CT, Xu YW, Peng YH. A Panel of Tumor-associated Autoantibodies for the Detection of Early-stage Breast Cancer. J Cancer 2021; 12:2747-2755. [PMID: 33854634 PMCID: PMC8040727 DOI: 10.7150/jca.57019] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 01/22/2021] [Indexed: 02/07/2023] Open
Abstract
We previously found a panel of autoantibodies against multiple tumor-associated antigens (BMI-1, HSP70, MMP-7, NY-ESO-1, p53 and PRDX6) that might facilitate early detection of esophagogastric junction adenocarcinoma and esophageal squamous cell carcinoma. Here we aimed at assessing the diagnostic performance of these autoantibodies in breast cancer patients. Enzyme-linked immunosorbent assay was applied to detect sera autoantibodies in 123 breast cancer patients and 123 age-matched normal controls. We adopted logistic regression analysis to identify optimized autoantibody biomarkers for diagnosis and receiver-operating characteristics to analyze diagnostic efficiency. Five of six autoantibodies, BMI-1, HSP70, NY-ESO-1, p53 and PRDX6 demonstrated significantly elevated serum levels in breast cancer compared to normal controls. An optimized panel composed of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 showed an area under the curve (AUC) of 0.819 (95% CI 0.766-0.873), 63.4% sensitivity and 90.2% specificity for diagnosing breast cancer. Moreover, this autoantibody panel could differentiate patients with early stage breast cancer from normal controls, with AUC of 0.805 (95% CI 0.743-0.886), 59.6% sensitivity and 90.2% specificity. Our findings indicated that the panel of autoantibodies to BMI-1, HSP70, NY-ESO-1 and p53 as serum biomarkers have the potential to help detect early stage breast cancer.
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Affiliation(s)
- Chao-Qun Hong
- Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xue-Fen Weng
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Xu-Chun Huang
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Ling-Yu Chu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Lai-Feng Wei
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yi-Wei Lin
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Liu-Yi Chen
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Can-Tong Liu
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yi-Wei Xu
- Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou 515041, Guangdong, China
| | - Yu-Hui Peng
- Guangdong Provincial Key Laboratory of Breast Cancer Diagnosis and Treatment, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Department of Clinical Laboratory Medicine, Cancer Hospital of Shantou University Medical College, Shantou 515041, Guangdong, China
- Precision Medicine Research Centre, Shantou University Medical College, Shantou 515041, Guangdong, China
- Guangdong Esophageal Cancer Research Institute, Shantou University Medical College, Shantou 515041, Guangdong, China
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Stability of interleukin-1β, -4, -6, -8, -10, -13, interferon-γ and tumor necrosis factor-α in human sera after repetitive freeze-thaw cycles and long storage. J Pharm Biomed Anal 2021; 196:113900. [PMID: 33535109 DOI: 10.1016/j.jpba.2021.113900] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 01/10/2021] [Accepted: 01/11/2021] [Indexed: 12/14/2022]
Abstract
INTRODUCTION Cytokines (CKs) are one of the key components of the molecular network modulating multiple immunological interactions. Within such biological systems, CKs functions are associated with several processes, thus quantification of these analytes in serum samples, as well as a faithful determination of its concentration, are crucial for the translational aspect of many studies. AIM This study is focused on the evaluation of the effects of storage duration and multiple freeze-thaw cycles on CKs stability. MATERIALS AND METHODS Serum samples were obtained from 24 healthy participants. Samples were prospectively stored at 4 °C for 1-7 and 30 days, and also underwent multiple freeze-thaw cycles. Afterwards, CK levels were determined by enzyme-linked immunosorbent assay. RESULTS Among the 8 examined CKs all of them showed significant degradation (determined with the two-way ANOVA and post-hoc test) after 4 days of sample storage at 4 °C. Serum were affected by freezing at -20 °C and thawing, and 2 of CKs (IL-1β and IL-8) showed significant concentration decrease after following 2 freeze-thaw cycles. It has been also determineded that CKs in serum samples after multiple freeze-thaw cycles had better stability, when samples were stored at -80 °C (compared to storage at -20 °C). CONCLUSIONS This study demonstrates that long storage at 4 °C, as well as multiple freeze-thaw cycles of serum samples, must be avoided and CK concentrations should be measured immediately after sample collection.
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Wei X, Chen K, Guo S, Liu W, Zhao XZ. Emerging Microfluidic Technologies for the Detection of Circulating Tumor Cells and Fetal Nucleated Red Blood Cells. ACS APPLIED BIO MATERIALS 2021; 4:1140-1155. [DOI: 10.1021/acsabm.0c01325] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Affiliation(s)
- Xiaoyun Wei
- Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China
- Key Laboratory of Medical Information and 3D Bioprinting of Zhejiang Province, Hangzhou Dianzi University, Hangzhou 310018, China
| | - Keke Chen
- Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China
| | - Shishang Guo
- Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China
| | - Wei Liu
- Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China
| | - Xing-Zhong Zhao
- Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, China
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48
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Vergis S, Bezas K, Exarchos TP. Decision Support System for Breast Cancer Detection Using Biomarker Indicators. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2021; 1338:13-19. [DOI: 10.1007/978-3-030-78775-2_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Jones AL, Dhanapala L, Baldo TA, Sharafeldin M, Krause CE, Shen M, Moghaddam S, Faria RC, Dey DK, Watson RW, Andrawis R, Lee NH, Rusling JF. Prostate Cancer Diagnosis in the Clinic Using an 8-Protein Biomarker Panel. Anal Chem 2020; 93:1059-1067. [PMID: 33289381 DOI: 10.1021/acs.analchem.0c04034] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The inability to distinguish aggressive from indolent prostate cancer is a longstanding clinical problem. Prostate specific antigen (PSA) tests and digital rectal exams cannot differentiate these forms. Because only ∼10% of diagnosed prostate cancer cases are aggressive, existing practice often results in overtreatment including unnecessary surgeries that degrade patients' quality of life. Here, we describe a fast microfluidic immunoarray optimized to determine 8-proteins simultaneously in 5 μL of blood serum for prostate cancer diagnostics. Using polymeric horseradish peroxidase (poly-HRP, 400 HRPs) labels to provide large signal amplification and limits of detection in the sub-fg mL-1 range, a protocol was devised for the optimization of the fast, accurate assays of 100-fold diluted serum samples. Analysis of 130 prostate cancer patient serum samples revealed that some members of the protein panel can distinguish aggressive from indolent cancers. Logistic regression was used to identify a subset of the panel, combining biomarker proteins ETS-related gene protein (ERG), insulin-like growth factor-1 (IGF-1), pigment epithelial-derived factor (PEDF), and serum monocyte differentiation antigen (CD-14) to predict whether a given patient should be referred for biopsy, which gave a much better predictive accuracy than PSA alone. This represents the first prostate cancer blood test that can predict which patients will have a high biopsy Gleason score, a standard pathology score used to grade tumors.
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Affiliation(s)
- Abby L Jones
- Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
| | - Lasangi Dhanapala
- Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
| | - Thaísa A Baldo
- Department of Chemistry, Federal University of São Carlos, São Carlos 13565-905, São Paulo, Brazil
| | - Mohamed Sharafeldin
- Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
| | - Colleen E Krause
- Department of Chemistry, University of Hartford, 200 Bloomfield Avenue, West Hartford, Connecticut 06117, United States
| | - Min Shen
- Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
| | - Shirin Moghaddam
- School of Mathematical Sciences, University College Cork, Cork T12YT20, Ireland
| | - Ronaldo C Faria
- Department of Chemistry, Federal University of São Carlos, São Carlos 13565-905, São Paulo, Brazil
| | - Dipak K Dey
- Department of Statistics, University of Connecticut, 215 Glenbrook Road, Storrs, Connecticut 06269, United States
| | - R William Watson
- Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin 4, Ireland.,UCD School of Medicine and Medical Science, University College Dublin, Dublin 4, Ireland
| | - Ramez Andrawis
- Department of Urology, George Washington University, 2300 I Street, NW, Washington, Washington, D.C. 20037, United States
| | - Norman H Lee
- Department of Pharmacology and Physiology, George Washington University, 2300 I Street, NW, Washington, Washington, D.C. 20037, United States.,GW Cancer Center, 800 22nd Street, NW, Washington, Washington, D.C. 20052, United States
| | - James F Rusling
- Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States.,School of Chemistry, National University of Ireland Galway, University Road, Galway H91 CF50, Ireland.,Institute of Materials Science, University of Connecticut, 97 N. Eagleville Road, Storrs, Connecticut 06269, United States.,Department of Surgery, UConn Health Center, Farmington, Connecticut 06232, United States
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Jafari D, Tiyuri A, Rezaei E, Moradi Y, Jafari R, Jokar Shoorijeh F, Barati M. Diagnostic accuracy of cerebrospinal fluid and serum-isolated extracellular vesicles for glioblastoma: a systematic review and meta-analysis. Expert Rev Mol Diagn 2020; 20:1075-1085. [PMID: 33131342 DOI: 10.1080/14737159.2020.1844006] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
BACKGROUND Glioblastoma (GBM) is the most malignant brain cancer because there are no available biopsy-free methods for the diagnosis or the preoperative early detection. In this regard, the development of a non- or minimally invasive methods for early detection could increase the survival rate of GBM patients. METHODS The present study aimed to assess the diagnostic accuracy of extracellular vesicles (EVs) derived RNAs, isolated from patients' CSF or serum for GBM diagnosis. For this purpose, we searched all literature databases and performed a backward and forward reference checking procedure to retrieve appropriate studies. We conducted a meta-analysis on EVs derived biomarkers as well as sensitivity analysis and meta-regression. RESULTS We identified EVs-derived 24 RNAs, which can diagnose GBM. The analyzed pooled data showed 76% sensitivity, 80% specificity, and 0.85 AUC, for 16 biomarkers. Besides, the pooled PLR, NLR, and DOR were 3.7, 0.30, and 12, respectively. Subgroup analysis did not show a significant difference between serum and CSF. CONCLUSIONS According to the pooled sensitivity, specificity, and AUC for EVs derived biomarkers, we suggest that EVs-derived biomarkers might serve as a high potential and noninvasive diagnostic tool for GBM detection using serum and CSF samples.
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Affiliation(s)
- Davod Jafari
- Student Research Committee, Faculty of Allied Medicine, Iran University of Medical Sciences , Tehran, Iran.,Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences , Tehran, Iran
| | - Amir Tiyuri
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences , Tehran, Iran
| | - Elmnaz Rezaei
- Department of Biotechnology, Faculty of Natural Sciences, Imam Khomeini International University , Qazvin, Iran
| | - Yousef Moradi
- Department of Epidemiology, School of Public Health, Iran University of Medical Sciences , Tehran, Iran
| | - Rasool Jafari
- Department of Medical Parasitology and Mycology, School of Medicine, Urmia University of Medical Sciences , Urmia, Iran
| | | | - Mahmood Barati
- Department of Medical Biotechnology, Faculty of Allied Medicine, Iran University of Medical Sciences , Tehran, Iran
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