• biomarkers
• metabolomics
• oral potentially malignant disorder
• oral squamous cell carcinoma

• FP020-2019A Ministry of Higher Education Malaysia

• Cancer diagnosis
• Endoscopy
• Machine learning
• Plasmonic materials
• Surface-enhance Raman scattering (SERS)

• Colorectal Neoplasms/diagnosis
• Colorectal Neoplasms/pathology
• Animals
• Machine Learning
• Gold/chemistry
• Spectrum Analysis, Raman/methods
• Humans
• Biosensing Techniques/instrumentation
• Metal Nanoparticles/chemistry
• Mice
• Needles
• Endoscopy/instrumentation

• MOF hybrids
• cancers
• laser desorption/ionization mass spectrometry
• metabolic profiling
• thyroid nodules

• Ammonia
• Colorectal cancer (CRC)
• Hydrogen sulphide (H(2)S)
• Indole compounds
• Metabolites
• Microbiota
• N-nitroso compounds (NOC)
• Phenolic compounds
• Polyamines
• Protein
• Trimethylamine N-oxide (TMAO)

• Colorectal Neoplasms/microbiology
• Colorectal Neoplasms/metabolism
• Colorectal Neoplasms/etiology
• Humans
• Gastrointestinal Microbiome
• Fermentation
• Risk Factors
• Diet
• Animals

• Biomarkers
• Electrospinning
• Mass spectrometry
• Polar metabolites
• Solid phase microextraction

• Mass Spectrometry
• Solid Phase Microextraction/methods

• bioorthogonal reaction
• cancer detection
• in vitro diagnosis
• ingestible probe
• urinalysis

• Biomarkers, Tumor/urine
• Animals
• Mice
• Humans
• Gastrointestinal Neoplasms/diagnosis
• Gastrointestinal Neoplasms/urine
• Urinalysis/methods
• Cell Line, Tumor
• Early Detection of Cancer/methods
• Fluorescent Dyes/chemistry
• Administration, Oral

• NRF-NRFI07-2021-0005 Singapore National Research Foundation
• MOE-T2EP30220-0010 Academic Research Fund
• MOE-T2EP30221-0004 Academic Research Fund

• Black raspberries
• TCA cycle
• benzoates
• familial adenomatous polyposis
• glutathione metabolism
• inositol metabolism
• metabolomics
• polyamine pathway

• R01 CA148818 NCI NIH HHS

• cancer
• diagnosis
• electronic nose
• microbiota
• pathway analysis
• volatile organic compounds

• Humans
• Volatile Organic Compounds/analysis
• Volatile Organic Compounds/urine
• Breath Tests
• Neoplasms/diagnosis
• Metabolic Networks and Pathways
• Exhalation

• Biomarkers
• body fluids
• carcinogenesis
• metabolites
• urine

• 20-carboxy-LTB4, 2-oxo-4-methylthio-butanoic acid
• acrosome reaction
• capacitation
• lipidomics
• male reproduction
• sperm function
• spermatozoa

• Humans
• Male
• Acrosome Reaction/physiology
• Lipidomics
• Semen
• Chromatography, Liquid
• Sperm Capacitation/physiology
• Tandem Mass Spectrometry
• Spermatozoa/physiology
• Lipids

• National Natural Science Foundation of China
• Natural Science Foundation of Zhejiang Province
• Zhejiang Provincial Program for the Cultivation of High-Level Innovative Health Talents

• Colorectal cancer
• Colorimetric assay
• Hippurate
• Urine
• p-toluenesulfonyl chloride

• Humans
• Colorimetry
• Body Fluids
• Biological Assay
• Hippurates

• UG3 EB024965 NIBIB NIH HHS

• Colorectal cancer
• Comprehensive gas chromatography
• GC × GC
• Metabolic correlations
• QC system
• Untargeted metabolomics

• Humans
• Metabolomics
• Gas Chromatography-Mass Spectrometry
• Colorectal Neoplasms/diagnosis

• Colorectal cancer screening
• cancer biomarkers
• liquid chromatography-mass spectrometry
• logistic regression
• metabolomic profiling
• urine test

• Humans
• Chromatography, Liquid/methods
• Early Detection of Cancer/methods
• Tandem Mass Spectrometry
• Biomarkers, Tumor/metabolism
• Colorectal Neoplasms/metabolism

• P30 CA008748 NCI NIH HHS
• UG3 EB024965 NIBIB NIH HHS
• UH3 CA257869 NCI NIH HHS

• colorectal cancer
• microbiota
• volatile organic compounds

• angiogenesis
• hypoxia-inducible factor 1-alpha (HIF1α)
• succinate
• succinate dehydrogenase (SDH)
• succinate receptor-1 (SUCNR1)

• DOC 31 Austrian Science Fund FWF

As the worldwide prevalence of colorectal cancer (CRC) increases, it is vital to reduce its morbidity and mortality through early detection. Saliva‐based tests are an ideal noninvasive tool for CRC detection. Here, we explored and validated salivary biomarkers to distinguish patients with CRC from those with adenoma (AD) and healthy controls (HC). Saliva samples were collected from patients with CRC, AD, and HC. Untargeted salivary hydrophilic metabolite profiling was conducted using capillary electrophoresis–mass spectrometry and liquid chromatography–mass spectrometry. An alternative decision tree (ADTree)‐based machine learning (ML) method was used to assess the discrimination abilities of the quantified metabolites. A total of 2602 unstimulated saliva samples were collected from subjects with CRC (n = 235), AD (n = 50), and HC (n = 2317). Data were randomly divided into training (n = 1301) and validation datasets (n = 1301). The clustering analysis showed a clear consistency of aberrant metabolites between the two groups. The ADTree model was optimized through cross‐validation (CV) using the training dataset, and the developed model was validated using the validation dataset. The model discriminating CRC + AD from HC showed area under the receiver‐operating characteristic curves (AUC) of 0.860 (95% confidence interval [CI]: 0.828‐0.891) for CV and 0.870 (95% CI: 0.837‐0.903) for the validation dataset. The other model discriminating CRC from AD + HC showed an AUC of 0.879 (95% CI: 0.851‐0.907) and 0.870 (95% CI: 0.838‐0.902), respectively. Salivary metabolomics combined with ML demonstrated high accuracy and versatility in detecting CRC.

• biomarker
• colorectal cancer
• metabolomics
• polyamine
• saliva

• Bowel cleansing
• Colonoscopy
• Inflammatory bowel disease
• Metabolomics
• Metabonomics
• Microbiome

• Feces/chemistry
• Gastrointestinal Microbiome
• Humans
• Intestines/microbiology
• Microbiota
• RNA, Ribosomal, 16S/analysis
• RNA, Ribosomal, 16S/genetics

• NIHR Imperial Biomedical Research Centre

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers with high mortality rate due to its poor diagnosis in the early stage. Here, we report a urinary metabolomic study on a cohort of CRC patients (n =67) and healthy controls (n =21) using ultraperformance liquid chromatography triple quadrupole mass spectrometry. Pathway analysis showed that a series of pathways that belong to amino acid metabolism, carbohydrate metabolism, and lipid metabolism were dysregulated, for instance the glycine, serine and threonine metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism, glycolysis, and TCA cycle. A total of 48 differential metabolites were identified in CRC compared to controls. A panel of 12 biomarkers composed of chenodeoxycholic acid, vanillic acid, adenosine monophosphate, glycolic acid, histidine, azelaic acid, hydroxypropionic acid, glycine, 3,4-dihydroxymandelic acid, 4-hydroxybenzoic acid, oxoglutaric acid, and homocitrulline were identified by Random Forest (RF), Support Vector Machine (SVM), and Boruta analysis classification model and validated by Gradient Boosting (GB), Logistic Regression (LR), and Random Forest diagnostic model, which were able to discriminate CRC subjects from healthy controls. These urinary metabolic biomarkers provided a novel and promising molecular approach for the early diagnosis of CRC.

Chemical communication plays a major role in social interactions. Cancer, by inducing changes in body odours, may alter interactions between individuals. In the framework of research targeting non-invasive methods to detect early stages of cancer development, this study asked whether untrained mice could detect odour changes in cancerous congeners. If yes, were they able to detect cancer at an early developmental stage? Did it influence female preference? Did variations in volatile organic components of the odour source paralleled mice behavioural responses? We used transgenic mice strains developing or not lung cancer upon antibiotic ingestion. We sampled soiled bedding of cancerous mice (CC) and not cancerous mice (NC), at three experimental conditions: before (T0), early stage (T2) and late stage (T12) of cancer development. Habituation/generalisation and two-way preference tests were performed where soiled beddings of CC and NC mice were presented to wild-derived mice. The composition and relative concentration of volatile organic components (VOC) in the two stimuli types were analysed. Females did not show directional preference at any of the experimental conditions, suggesting that cancer did not influence their choice behaviour. Males did not discriminate between CC and NC stimuli at T0 but did so at T2 and T12, indicating that wild-derived mice could detect cancer at an early stage of development. Finally, although the VOC bouquet differed between CC and NC it did not seem to parallel the observed behavioural response suggesting that other types of odorant components might be involved in behavioural discrimination between CC and NC mice.

Summary: Male mice could discriminate the smell of cancerous congeners even when the tumour was hardly detectable by other means; however, females did not discriminate against the smell of males carrying cancerous tumours. Odorant molecules other than volatile organic compounds analysed here might explain the observed behaviour.

• Mus musculus domesticus
• Body odours
• EGFR oncogenic mutation
• Female preference
• Lung cancer
• Odour discrimination
• Volatile organic compounds

• chemotherapy
• colorectal cancer
• metabolomics
• prognostic value
• surgery

• High-protein diet
• Metabolomics
• UHPLC-MS

• Animals
• Biomarkers/urine
• Body Weight
• Chromatography, High Pressure Liquid/methods
• Diet, High-Protein
• Dietary Proteins/metabolism
• Male
• Mass Spectrometry/methods
• Metabolomics/methods
• Muscle, Skeletal/chemistry
• Muscle, Skeletal/metabolism
• Rats
• Rats, Wistar
• Time Factors
• Urine/chemistry

The incidence of young people <50 years old who are diagnosed with colorectal cancer (CRC), termed as early onset colorectal cancer (EOCRC), accounted for nearly 30% of the total CRC patients in Indonesia, which is about three times higher than what is being reported in Europe, the UK and USA. Lynch syndrome (LS) is a hereditary type of CRC that is associated with a younger age of onset. Detecting LS has been long reported to be a cost-effective strategy to provide aid in the diagnosis or management of the individual or at-risk family members. The aim of this retrospective study was to screen for Lynch Syndrome in Indonesian CRC patients using simple and robust polymerase chain reaction (PCR)-based molecular testing, known as N_LyST (Nottingham Lynch Syndrome Test). To our knowledge, we are the first to study and observe a potentially higher frequency of LS (13.85%) among CRC patients in Indonesia (n = 231). This may partially contribute to the reported much higher rate of EOCRC found in the country.

There is about three times higher incidence of young patients <50 years old with colorectal cancer, termed EOCRC, in Indonesia as compared to Europe, the UK and USA. The aim of this study was to investigate the frequency of Lynch Syndrome (LS) in Indonesian CRC patients. The previously described Nottingham Lynch Syndrome Test (N_LyST) was used in this project. N_LyST is a robust high-resolution melting (HRM)-based test that has shown 100% concordance with standard reference methods, including capillary electrophoresis and Sanger sequencing. The test consisted of five mononucleotide microsatellite markers (BAT25, BAT26, BCAT25, MYB, EWSR1), BRAF V600E mutation and MLH1 region C promoter for methylation (using bisulphite-modified DNA). A total of 231 archival (2016–2019) formalin-fixed, paraffin-embedded (FFPE) tumour tissues from CRC patients collected from Dr. Sardjito General Hospital Yogyakarta, Indonesia, were successfully tested and analysed. Among those, 44/231 (19.05%) were MSI, 25/231 (10.82%) were harbouring BRAF V600E mutation and 6/231 (2.60%) had MLH1 promoter methylation. Almost all—186/197 (99.45%)—MSS cases were MLH1 promoter unmethylated, while there were only 5/44 (11.36%) MSI cases with MLH1 promoter methylation. Similarly, only 9/44 (20.45%) of MSI cases were BRAF mutant. There were 50/231 (21.65%) EOCRC cases, with 15/50 (30%) regarded as MSI, as opposed to 29/181 (16.02%) within the older group. In total, 32/231 patients (13.85%) were classified as “Probable Lynch” (MSI, BRAF wildtype and MLH1 promoter unmethylated), which were enriched in EOCRC as compared to older patients (24% vs. 11.05%, p = 0.035). Nonetheless, 30/50 (76.00%) cases among the EOCRC cases were non-LS (sporadic) and were significantly associated with a left-sided tumour. The overall survival of both “Probable Lynch” and non-LS (sporadic) groups (n = 227) was comparable (p = 0.59), with follow up period of 0–1845 days/61.5 months. Stage, node status, histological grading and ECOG score were significantly associated with patient overall survival (p < 0.005), yet only ECOG was an independent factor for OS (HR: 4.38; 95% CI: 1.72–11.2; p = 0.002). In summary, this study is the first to reveal a potentially higher frequency of LS among CRC patients in Indonesia, which may partially contribute to the reported much higher number of EOCRC as compared to the incidence in the West.

• Biomarker
• Cancer
• Diagnostics
• Odors
• Volatile organic compound

• infantile hemangioma
• metabolic profiling
• prediction biomarker
• umbilical cord blood serum

• colorectal cancer
• meta-analysis
• metabolomics
• systematic review
• urine
• volatilomics

• RTI2018-098577-B-C21 Spanish National Plan for Scientific and Technical Research and Innovation
• RTI2018-098577-B-C22 Spanish National Plan for Scientific and Technical Research and Innovation
• 2018LLAV00072 Agència de Gestió d'Ajuts Universitaris i de Recerca
• 798038 H2020 Marie Skłodowska-Curie Actions
• APIF_18_19 Universitat de Barcelona
• 2019PMF-PIPF-37 Universitat Rovira i Virgili
• 2017 SGR 1721 Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
• 2017 SGR 1119 Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
• CA17118 European Cooperation in Science and Technology

Metabolomics data analysis depends on the utilization of bioinformatics tools. To meet the evolving needs of metabolomics research, several integrated platforms have been developed. Our group has developed a desktop platform IP4M (integrated Platform for Metabolomics Data Analysis) which allows users to perform a nearly complete metabolomics data analysis in one-stop. With the extensive usage of IP4M, more and more demands were raised from users worldwide for a web version and a more customized workflow. Thus, iMAP (integrated Metabolomics Analysis Platform) was developed with extended functions, improved performances, and redesigned structures. Compared with existing platforms, iMAP has more methods and usage modes. A new module was developed with an automatic pipeline for train-test set separation, feature selection, and predictive model construction and validation. A new module was incorporated with sufficient editable parameters for network construction, visualization, and analysis. Moreover, plenty of plotting tools have been upgraded for highly customized publication-ready figures. Overall, iMAP is a good alternative tool with complementary functions to existing metabolomics data analysis platforms. iMAP is freely available for academic usage at https://imap.metaboprofile.cloud/ (License MPL 2.0).

• correlation-based network
• metabolomics
• statistical analysis
• visualization
• workflow

• CPMG
• Human synovial fluid
• NMR spectroscopy
• NOESYGPPR1D
• Sample storage
• Temperature

• biomarkers
• metabolic profiling
• metabonomics
• neuroendocrine neoplasms
• neuroendocrine tumours
• nuclear magnetic resonance
• precision medicine

Colorectal cancer (CRC) has increasing global prevalence and poor prognostic outcomes, and the development of low- or less invasive screening tests is urgently required. Urine is an ideal biofluid that can be collected non-invasively and contains various metabolite biomarkers. To understand the metabolomic profiles of different stages of CRC, we conducted metabolomic profiling of urinary samples. Capillary electrophoresis-time-of-flight mass spectrometry was used to quantify hydrophilic metabolites in 247 subjects with stage 0 to IV CRC or polyps, and healthy controls. The 154 identified and quantified metabolites included metabolites of glycolysis, TCA cycle, amino acids, urea cycle, and polyamine pathways. The concentrations of these metabolites gradually increased with the stage, and samples of CRC stage IV especially showed a large difference compared to other stages. Polyps and CRC also showed different concentration patterns. We also assessed the differentiation ability of these metabolites. A multiple logistic regression model using three metabolites was developed with a randomly designated training dataset and validated using the remaining data to differentiate CRC and polys from healthy controls based on a panel of urinary metabolites. These data highlight the changes in metabolites from early to late stage of CRC and also the differences between CRC and polyps.

There are currently no effective specific biomarkers for the screening of early gastric cancer. Recently, metabolomics has been used to profile small endogenous metabolites, demonstrating significant potential in the diagnosis/screening of cancer, owing to its ability to conduct a noninvasive sample analysis. Here, we performed a urine metabolomics analysis in the context of an early diagnosis of gastric cancer. This approach showed very high diagnostic sensitivity and specificity and performed significantly better than the analysis of serum tumor markers modalities. An additional genomic data analysis revealed the up-regulation of several genes in gastric cancer. This metabolomics-based early diagnosis approach may have the potential for mass screening an average-risk population and may facilitate endoscopic examination through risk stratification.

The early detection of gastric cancer (GC) could decrease its incidence and mortality. However, there are currently no accurate noninvasive markers for GC screening. Therefore, we developed a noninvasive diagnostic approach, employing urine nuclear magnetic resonance (NMR) metabolomics, to discover putative metabolic markers associated with GC. Changes in urine metabolite levels during oncogenesis were evaluated using samples from 103 patients with GC and 100 age- and sex-matched healthy controls. Approximately 70% of the patients with GC (n = 69) had stage I GC, with the majority (n = 56) having intramucosal cancer. A multivariate statistical analysis of the urine NMR data well discriminated between the patient and control groups and revealed nine metabolites, including alanine, citrate, creatine, creatinine, glycerol, hippurate, phenylalanine, taurine, and 3-hydroxybutyrate, that contributed to the difference. A diagnostic performance test with a separate validation set exhibited a sensitivity and specificity of more than 90%, even with the intramucosal cancer samples only. In conclusion, the NMR-based urine metabolomics approach may have potential as a convenient screening method for the early detection of GC and may facilitate consequent endoscopic examination through risk stratification.

• gastric cancer
• metabolomics
• screening
• urine

• UHPLC-Q-TOF-MS
• adverse effect
• capecitabine
• colorectal cancer
• untargeted metabolomics

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. In Europe, it is the second most common cause of cancer-related deaths. With the advent of metabolomics approaches, studies regarding the investigation of metabolite profiles related to CRC have been conducted, aiming to serve as a tool for early diagnosis. In order to provide further information about the current status of this field of research, 21 studies were systematically reviewed, regarding their main findings and analytical aspects. A special focus was given to the employment of matrices obtained non-invasively and the use of gas chromatography as the analytical platform. The relationship between the reported volatile and non-volatile biomarkers and CRC-related metabolic alterations was also explored, demonstrating that many of these metabolites are connected with biochemical pathways proven to be involved in carcinogenesis. The most commonly reported CRC indicators were hydrocarbons, aldehydes, amino acids and short-chain fatty acids. These potential biomarkers can be associated with both human and bacterial pathways and the analysis based on such species has the potential to be applied in the clinical practice as a low-cost screening method.

• VOCs
• biomarker
• breath
• colorectal cancer
• feces
• gas chromatography
• pathways
• profiling
• urine

• 2DLC-MS
• GC × GC-MS
• case-control study
• colorectal cancer
• untargeted metabolomics

• P30CA022453; R01CA93817; 1P20GM113226; S10OD020106. NIH HHS

The progress in the discovery and validation of metabolite biomarkers for the detection of colorectal cancer (CRC) has been hampered by the lack of reproducibility between study cohorts. The majority of discovery-phase biomarker studies have used patient blood samples to identify disease-related metabolites, but this pre-validation phase is confounded by non-specific disease influences on the metabolome. We therefore propose that metabolite biomarker discovery would have greater success and higher reproducibility for CRC if the discovery phase was conducted in tumor tissues, to find metabolites that have higher specificity to the metabolic consequences of the disease, that are then validated in blood samples. This would thereby eliminate any non-tumor and/or body response effects to the disease. In this study, we performed comprehensive untargeted metabolomics analyses on normal (adjacent) colon and tumor tissues from CRC patients, revealing tumor tissue-specific biomarkers (n = 39/group). We identified 28 highly discriminatory tumor tissue metabolite biomarkers of CRC by orthogonal partial least-squares discriminant analysis (OPLS-DA) and univariate analyses (VIP > 1.5, p < 0.05). A stepwise selection procedure was used to identify nine metabolites that were the most predictive of CRC with areas under the curve (AUCs) of >0.96, using various models. We further identified five biomarkers that were specific to the anatomic location of tumors in the colon (n = 236). The combination of these five metabolites (S-adenosyl-L-homocysteine, formylmethionine, fucose 1-phosphate, lactate, and phenylalanine) demonstrated high differentiative capability for left- and right-sided colon cancers at stage I by internal cross-validation (AUC = 0.804, 95% confidence interval, CI 0.670–0.940). This study thus revealed nine discriminatory biomarkers of CRC that are now poised for external validation in a future independent cohort of samples. We also discovered a discrete metabolic signature to determine the anatomic location of the tumor at the earliest stage, thus potentially providing clinicians a means to identify individuals that could be triaged for additional screening regimens.

• colorectal cancer (CRC)
• metabolite biomarkers
• metabolomics

Osteoarthritis (OA) is a multifactorial disease contributing to significant disability and economic burden in Western populations. The aetiology of OA remains poorly understood, but is thought to involve genetic, mechanical and environmental factors. Currently, the diagnosis of OA relies predominantly on clinical assessment and plain radiographic changes long after the disease has been initiated. Recent advances suggest that there are changes in joint fluid metabolites that are associated with OA development. If this is the case, biochemical and metabolic biomarkers of OA could help determine prognosis, monitor disease progression and identify potential therapeutic targets. Moreover, for focussed management and personalised medicine, novel biomarkers could sub-stratify patients into OA phenotypes, differentiating metabolic OA from post-traumatic, age-related and genetic OA. To date, OA biomarkers have concentrated on cytokine action and protein signalling with some progress. However, these remain to be adopted into routine clinical practice. In this review, we outline the emerging metabolic links to OA pathogenesis and how an elucidation of the metabolic changes in this condition may provide future, more descriptive biomarkers to differentiate OA subtypes.

• Metabolic profiling
• Metabolomics
• Metabonomics
• Osteoarthritis
• Personalised medicine

• multi-block partial least-squares analysis (MB-PLS)
• pathway importance in projection (PIP)
• significant metabolic pathway
• simulated pathway analysis

• Least-Squares Analysis
• Metabolic Networks and Pathways
• Metabolomics

• P30 CA015704 NCI NIH HHS

• Colorectal cancer
• microbiome
• tryptophan metabolism, volatile organic compounds mechanism
• urinary biomarker
• urine volatile organic compounds

• metabolomics
• microbiome
• omics integration

Surgery is the primary curative treatment for patients with nonmetastasized colorectal cancer (CRC). Rate of complications, morbidity, mortality, and overall survival of patients with CRC are factors associated with speed of recovery following surgery. Wuda granule (WD) is a traditional Chinese medicine (TCM) prescription used to promote rapid recovery after surgery. However, the specific mechanism of action of WD has not been characterized. Our study included 60 patients with clear histopathological evidence of colon or rectal cancer who underwent CRC laparoscopic surgery and 30 healthy individuals. Serum biochemistry and clinical evaluation of gastrointestinal function showed that WD could improve the nutritional status and gastrointestinal function and reduce the level of inflammation of patients with CRC following laparoscopic surgery. In addition, we used UPLC/Q-TOF-MS/MS-based metabolomics analysis to determine the mechanism of WD-related rapid recovery following laparoscopic surgery in patients with CRC. Twenty metabolites associated with arachidonic acid, alanine, aspartate and glutamate, α-linolenic acid, pyruvate, histidine, and glycerophospholipids were identified. The results suggested that the therapeutic mechanism of laparoscopic surgery combined with WD may be related to regulation of nutritional status, inflammation, immune function, energy, and gastrointestinal function in patients with CRC. This study also highlighted the ability of TCM compounds to interact with multiple targets to induce synergistic effects. This study may result in further studies of WD as a therapeutic agent to promote recovery following surgical resection of CRC tumors.

• Bacterial driver-passenger model
• Colorectal cancer metabolome
• Colorectal cancer microbiome
• Genome-scale metabolic models

• CNPQ
• Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Breast cancer (BC) remains the most frequent type of cancer in females worldwide. However, the pathogenesis of BC is still under the cloud, along with the huge challenge of early diagnosis, which is widely acknowledged as the key to a successful therapy. Metabolomics, a newborn innovative technique in recent years, has demonstrated great potential in cancer-related researches. The aim of this review is to look back on clinical and cellular metabolomic studies in the diagnosis of BC over the past decade, and provide a systematic summary of metabolic biomarkers and pathways related to BC diagnosis.

• Breast Cancer
• Diagnosis
• Metabolomics

Proton pump inhibitors (PPIs) are used for the long-term treatment of gastroesophageal disorders and the non-prescription medicines for acid reflux. However, there is growing concerns about PPI misuse, overuse and abuse. This study aimed to develop an animal model to examine the effects of long-term use of PPI in vivo. Twenty one Wistar rats were given omeprazole orally or intravenously for 30 days, and caerulein as a positive control. After euthanization, the serum and stool were collected to perform MS-based quantitative analysis of metabolites. We carried out 16S-based profiling of fecal microbiota, assessed the expression of bile acid metabolism regulators and examined the immunopathological characteristics of bile ducts. After long-term PPI exposure, the fecal microbial profile was altered and showed similarity to those observed in high-fat diet studies. The concentrations of several metabolites were also changed in various specimens. Surprisingly, morphological changes were observed in the bile duct, including ductal epithelial proliferation, micropapillary growth of biliary epithelium, focal bile duct stricture formation and bile duct obstruction. These are characteristics of precancerous lesions of bile duct. FXR and RXRα expressions were significantly reduced, which were similar to that observed in cholangiocarcinoma in TCGA and Oncomine databases. We established a novel animal model to examine the effects of long-term use of omeprazole. The gut microbes and metabolic change are consequences of long-term PPI exposure. And the results showed the environment in vivo tends to a high-fat diet. More importantly, we observed biliary epithelial hyperplasia, which is an indicator of a high-fat diet.

• LC-MS/MS
• Rhizopus nigricans
• azoxymethane/dextran sulfate sodium
• exopolysaccharide
• metabolomics
• colorectal cancer