American Association for Cancer Research
10780432ccr181515-sup-201689_3_supp_5377736_pnt80s.pdf (174.25 kB)

Supplementary Tble S3 from Multi-omics Integration Analysis Robustly Predicts High-Grade Patient Survival and Identifies CPT1B Effect on Fatty Acid Metabolism in Bladder Cancer

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journal contribution
posted on 2023-03-31, 20:41 authored by Venkatrao Vantaku, Jianrong Dong, Chandrashekar R. Ambati, Dimuthu Perera, Sri Ramya Donepudi, Chandra Sekhar Amara, Vasanta Putluri, Shiva Shankar Ravi, Matthew J. Robertson, Danthasinghe Waduge Badrajee Piyarathna, Mariana Villanueva, Friedrich-Carl von Rundstedt, Balasubramanyam Karanam, Leomar Y. Ballester, Martha K. Terris, Roni J. Bollag, Seth P. Lerner, Andrea B. Apolo, Hugo Villanueva, MinJae Lee, Andrew G. Sikora, Yair Lotan, Arun Sreekumar, Cristian Coarfa, Nagireddy Putluri

Supplementary Table S3. Patient characteristics of bladder specimens used for the metabolomics and lipidomics profiling.






Alkek Center for Molecular Discovery



The perturbation of metabolic pathways in high-grade bladder cancer has not been investigated. We aimed to identify a metabolic signature in high-grade bladder cancer by integrating unbiased metabolomics, lipidomics, and transcriptomics to predict patient survival and to discover novel therapeutic targets. We performed high-resolution liquid chromatography mass spectrometry (LC-MS) and bioinformatic analysis to determine the global metabolome and lipidome in high-grade bladder cancer. We further investigated the effects of impaired metabolic pathways using in vitro and in vivo models. We identified 519 differential metabolites and 19 lipids that were differentially expressed between low-grade and high-grade bladder cancer using the NIST MS metabolomics compendium and lipidblast MS/MS libraries, respectively. Pathway analysis revealed a unique set of biochemical pathways that are highly deregulated in high-grade bladder cancer. Integromics analysis identified a molecular gene signature associated with poor patient survival in bladder cancer. Low expression of CPT1B in high-grade tumors was associated with low FAO and low acyl carnitine levels in high-grade bladder cancer, which were confirmed using tissue microarrays. Ectopic expression of the CPT1B in high-grade bladder cancer cells led to reduced EMT in in vitro, and reduced cell proliferation, EMT, and metastasis in vivo. Our study demonstrates a novel approach for the integration of metabolomics, lipidomics, and transcriptomics data, and identifies a common gene signature associated with poor survival in patients with bladder cancer. Our data also suggest that impairment of FAO due to downregulation of CPT1B plays an important role in the progression toward high-grade bladder cancer and provide potential targets for therapeutic intervention.