The current system to predict the outcome of smokers with Bladder cancer (BLCA) is insufficient due to complex genomic and transcriptomic heterogeneities. This study aims to identify serum metabolite associated genes related to survival in this population.
We performed liquid chromatography-mass spectrometry (LC-MS) based targeted metabolomic analysis for >300 metabolites in serum obtained from two independent cohorts of BLCA 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 TCGA to obtain an intersecting signature specific for BLCA smokers.
40 metabolites (FDR <0.25) were identified to be differential between BLCA never smokers and smokers. Increased abundance of amino acids (tyrosine, phenylalanine, proline, serine, valine, isoleucine, glycine, asparagine) and taurine were observed in BLCA 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 BLCA smokers. Importantly, Catechol-O-Methyltransferase (COMT), Iodotyrosine Deiodinase (IYD), and Tubulin Tyrosine Ligase (TTL) showed a significant association with patient survival in publicly available BLCA smokers datasets and did not have any clinical association in never smokers.
Serum metabolic profiling of BLCA smokers revealed dysregulated amino acid metabolism. It provides a distinct gene signature that shows a prognostic value in predicting BLCA smoker survival.
Serum metabolic signature derived genes act as a predictive tool for studying the BLCA progression in smokers.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2019 Jan 14 [Epub ahead of print]
Chandra Sekhar Amara, Chandrashekar R Ambati, Venkatrao Vantaku, Danthasinghe Waduge Badrajee Piyarathna, Sri Ramya Donepudi, Shiva Shankar Ravi, James M Arnold, Vasanta Putluri, Gurkamal Chatta, Khurshid A Guru, Hoda Badr, Martha K Terris, Roni J Bollag, Arun Sreekumar, Andrea B Apolo, Nagireddy Putluri
Department of Molecular and Cell Biology, Baylor College of Medicine., Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine., Molecular and Cellular Biology, Baylor College of Medicine., Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine., Department of Medicine, Roswell Park Comprehensive Cancer Center., Department of Urology, Roswell Park Comprehensive Cancer Center., Department of Medicine, Baylor College of Medicine., Augusta University., Department of Molecular and Cell Biology and Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine., Genitourinary Malignancy Branch, National Cancer Institute., Department of Molecular and Cell Biology, Baylor College of Medicine .