Dataset Information

Serum Metabolic Profiling Identified a Distinct Metabolic Signature in Bladder Cancer Smokers: A Key Metabolic Enzyme Associated with Patient Survival.

ABSTRACT: BACKGROUND:The current system to predict the outcome of smokers with bladder cancer is insufficient due to complex genomic and transcriptomic heterogeneities. This study aims to identify serum metabolite-associated genes related to survival in this population. METHODS:We performed LC/MS-based targeted metabolomic analysis for >300 metabolites in serum obtained from two independent cohorts of bladder cancer never smokers, smokers, healthy smokers, and healthy never smokers. A subset of differential metabolites was validated using Biocrates absoluteIDQ p180 Kit. Genes associated with differential metabolites were integrated with a publicly available cohort of The Cancer Genome Atlas (TCGA) to obtain an intersecting signature specific for bladder cancer smokers. RESULTS:Forty metabolites (FDR < 0.25) were identified to be differential between bladder cancer never smokers and smokers. Increased abundance of amino acids (tyrosine, phenylalanine, proline, serine, valine, isoleucine, glycine, and asparagine) and taurine were observed in bladder cancer smokers. Integration of differential metabolomic gene signature and transcriptomics data from TCGA cohort revealed an intersection of 17 genes that showed significant correlation with patient survival in bladder cancer smokers. Importantly, catechol-O-methyltransferase, iodotyrosine deiodinase, and tubulin tyrosine ligase showed a significant association with patient survival in publicly available bladder cancer smoker datasets and did not have any clinical association in never smokers. CONCLUSIONS:Serum metabolic profiling of bladder cancer smokers revealed dysregulated amino acid metabolism. It provides a distinct gene signature that shows a prognostic value in predicting bladder cancer smoker survival. IMPACT:Serum metabolic signature-derived genes act as a predictive tool for studying the bladder cancer progression in smokers.

SUBMITTER: Amara CS

PROVIDER: S-EPMC6449217 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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Serum Metabolic Profiling Identified a Distinct Metabolic Signature in Bladder Cancer Smokers: A Key Metabolic Enzyme Associated with Patient Survival.

Amara Chandra Sekhar CS Ambati Chandrashekar R CR Vantaku Venkatrao V Badrajee Piyarathna Danthasinghe Waduge DW Donepudi Sri Ramya SR Ravi Shiva Shankar SS Arnold James M JM Putluri Vasanta V Chatta Gurkamal G Guru Khurshid A KA Badr Hoda H Terris Martha K MK Bollag Roni J RJ Sreekumar Arun A Apolo Andrea B AB Putluri Nagireddy N

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20190114 4

<h4>Background</h4>The current system to predict the outcome of smokers with bladder cancer is insufficient due to complex genomic and transcriptomic heterogeneities. This study aims to identify serum metabolite-associated genes related to survival in this population.<h4>Methods</h4>We performed LC/MS-based targeted metabolomic analysis for >300 metabolites in serum obtained from two independent cohorts of bladder cancer never smokers, smokers, healthy smokers, and healthy never smokers. A subse ...[more]

PMID: 30642841

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Project description:BACKGROUND:Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF. Metabolic signatures might indicate pathological pathways involved in disease development and progression. Reliable serum biomarker would help to improve both diagnostic approach and monitoring of drug effects. METHOD:The global metabolic profiles measured by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) of ten stable IPF patients were compared to the ones of ten healthy participants. The results were validated in an additional study of eleven IPF patients and ten healthy controls. RESULTS:We discovered 10 discriminative metabolic features using multivariate and univariate statistical analysis. Among them, we identified one metabolite at a retention time of 9.59 min that was two times more abundant in the serum of IPF patients compared to healthy participants. Based on its ion pattern, a lysophosphatidylcholine (LysoPC) was proposed. LysoPC is a precursor of lysophosphatidic acid (LPA) - a known mediator for lung fibrosis with its pathway currently being evaluated as new therapeutic drug target for IPF and other fibrotic diseases. CONCLUSIONS:We identified a LysoPC by UHPLC-HRMS as potential biomarker in serum of patients with IPF. Further validation studies in a larger cohort are necessary to determine its role in IPF. TRIAL REGISTRATION:Serum samples from IPF patients have been obtained within the clinical trial NCT02173145 at baseline and from the idiopathic interstitial pneumonia (IIP) cohort study. The study was approved by the Swiss Ethics Committee, Bern (KEK 002/14 and 246/15 or PB_2016-01524).

Dataset Information

Serum Metabolic Profiling Identified a Distinct Metabolic Signature in Bladder Cancer Smokers: A Key Metabolic Enzyme Associated with Patient Survival.

Publications

Serum Metabolic Profiling Identified a Distinct Metabolic Signature in Bladder Cancer Smokers: A Key Metabolic Enzyme Associated with Patient Survival.

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