Abstract 2217: Serum metabolic profiling identified a distinct metabolic signature in bladder cancer smokers: A key metabolic enzymes associated with patient survival

Abstract

Abstract Urinary bladder cancer (BLCA) is the 9th most common malignant disease and the 13th most common cause of cancer death worldwide. Occupational exposure to carcinogens has been long associated with increased BLCA risk. Tobacco smoke contains more than 60 carcinogens causing at least 18 different types of cancer including BLCA. Reliable biomarkers for accurately predicting survival in Bladdder cancer (BLCA) smokers is lacking due to complex genomic and transcriptomic heterogeneities associated with the disease. 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. 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 levels were observed in BLCA smokers. Integration of differential metabolomic gene signature and transcriptomics from TCGA cohort resulted in intersecting 17 gene signature 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. Note: This abstract was not presented at the meeting. Citation Format: Chandra S. Amara, Chandrashekar R. Ambati, Venkatrao Vantaku, Piyarathna W b Danthasinghe, Sri Ramya Donepudi, Shiva S. Ravi, James M. Arnold, Vasantha Putluri, Gurkamal Chatta, Khurshid A. Guru, Hoda Badr, Martha K. Terris, Roni Bollag, Arun Sreekumar, Andrea B. Apolo, Nagireddy Putluri. Serum metabolic profiling identified a distinct metabolic signature in bladder cancer smokers: A key metabolic enzymes associated with patient survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2217.