Distinct Lipidomic Landscapes Associated with Clinical Stages of Urothelial Cancer of the Bladder.

The first global lipidomic profiles associated with urothelial cancer of the bladder (UCB) and its clinical stages associated with progression were identified.

To identify lipidomic signatures associated with survival and different clinical stages of UCB.

Pathologically confirmed 165 bladder-derived tissues (126 UCB, 39 benign adjacent or normal bladder tissues). UCB tissues included Ta (n=16), T1 (n=30), T2 (n=43), T3 (n=27), and T4 (n=9); lymphovascular invasion (LVI) positive (n=52) and negative (n=69); and lymph node status N0 (n=28), N1 (n=11), N2 (n=9), N3 (n=3), and Nx (n=75).

UCB tissues have higher levels of phospholipids and fatty acids, and reduced levels of triglycerides compared with benign tissues. A total of 59 genes associated with altered lipids in UCB strongly correlate with patient survival in an UCB public dataset. Within UCB, there was a progressive decrease in the levels of phosphatidylserine (PS), phosphatidylethanolamines (PEs), and phosphocholines, whereas an increase in the levels of diacylglycerols (DGs) with tumor stage. Transcript and protein expression of phosphatidylserine synthase 1, which converts DGs to PSs, decreased progressively with tumor stage. Levels of DGs and lyso-PEs were significantly elevated in tumors with LVI and lymph node involvement, respectively. Lack of carcinoma in situ and treatment information is the limitation of our study.

To date, this is the first study describing the global lipidomic profiles associated with UCB and identifies lipids associated with tumor stages, LVI, and lymph node status. Our data suggest that triglycerides serve as the primary energy source in UCB, while phospholipid alterations could affect membrane structure and/or signaling associated with tumor progression.

Lipidomic alterations identified in this study set the stage for characterization of pathways associated with these altered lipids that, in turn, could inform the development of first-of-its-kind lipid-based noninvasive biomarkers and novel therapeutic targets for aggressive urothelial cancer of the bladder.

European urology focus. 2017 Apr 20 [Epub ahead of print]

Danthasinghe Waduge Badrajee Piyarathna, Thekkelnaycke M Rajendiran, Vasanta Putluri, Venkatrao Vantaku, Tanu Soni, Friedrich-Carl von Rundstedt, Sri Ramya Donepudi, Feng Jin, Suman Maity, Chandrashekar R Ambati, Jianrong Dong, Daniel Gödde, Stephan Roth, Stephan Störkel, Stephan Degener, George Michailidis, Seth P Lerner, Subramaniam Pennathur, Yair Lotan, Cristian Coarfa, Arun Sreekumar, Nagireddy Putluri

Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA., Department of Pathology, Michigan Regional Comprehensive Metabolomics Resource Core, Ann Arbor, Michigan, USA; Division of Bioinformatics, Michigan Regional Comprehensive Metabolomics Resource Core, Ann Arbor, Michigan, USA., Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA., Division of Bioinformatics, Michigan Regional Comprehensive Metabolomics Resource Core, Ann Arbor, Michigan, USA., Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA; Department of Urology, Jena University Hospital, Friedrich-Schiller-University, Jena, Germany., Department of Pathology, Witten-Herdecke University, Wuppertal, Germany., Department of Urology Helios Klinikum, Witten-Herdecke University, Wuppertal, Germany., Department of Statistics, University of Florida, Gainesville, FL, USA., Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA., Division of Nephrology, Department of Medicine, University of Michigan, Ann Arbor MI 48015., Department of Urology, University of Texas Southwestern, Dallas, TX, USA., Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA., Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA; Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, TX, USA., Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX, USA; Dan L. Duncan Cancer Center, Advanced Technology Core, Alkek Center for Molecular Discovery, Baylor College of Medicine, Houston, TX, USA. Electronic address: .