Year: 2018
Type: article
Study design: Observational Study
Abstract: You have accessJournal of UrologyKidney Cancer: Basic Research & Pathophysiology III1 Apr 2018MP88-03 USE OF URINARY METABOLOMICS TO IDENTIFY HIGH-RISK CLEAR CELL RENAL CELL CARCINOMA Mohit Gupta, Hiten Patel, Alice Semerjian, Michael Gorin, Michael Johnson, Mohamad Allaf, and Phillip Pierorazio Mohit GuptaMohit Gupta More articles by this author , Hiten PatelHiten Patel More articles by this author , Alice SemerjianAlice Semerjian More articles by this author , Michael GorinMichael Gorin More articles by this author , Michael JohnsonMichael Johnson More articles by this author , Mohamad AllafMohamad Allaf More articles by this author , and Phillip PierorazioPhillip Pierorazio More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2923AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Metabolomics offers the ability to exploit the unique metabolic dysregulation inherent in known pathways of renal cell carcinoma pathogenesis to help guide clinical management. While metabolomic pathways and signatures have been studied of a variety of cancers, the signature of urine of patients with RCC has not been well established. We consequently interrogated distinct urinary pathway-level metabolic shifts in patients following surgical excision of renal masses to differentiate metabolic profiles of high-risk clear cell RCC (ccRCC) from indolent and benign tumors. METHODS Patients undergoing surgery for non-metastatic RCC were enrolled in an IRB-approved, institutional biorepository and donated urine samples prior to surgery. Patients′ pathology was indexed as high-risk (HR), defined as high-grade (Grade III-IV) and/or locally-advanced (pT3 or higher) ccRCC; indolent, defined as pT1-T2 and low-grade (Grade I-II) ccRCC; or benign. Capillary electrophoresis mass spectrometry was utilized to process urine samples in a high-throughput fashion to identify distinctive metabolomic profiles indicative of the three pathologies. Sixty-nine targeted metabolites were detected and quantified; principal components analysis and heatmaps were generated. Differences were analyzed using Welch′s t-test. RESULTS A total of 66 urine specimens were included in our analysis: 30 (45.4%) were from patients with HR RCC, 19 (28.8%) from patients with indolent disease, and 17 (25.8%) from patients with benign pathology. Patients with indolent lesions had higher concentrations of the following unique amino acids compared to benign lesions (p<0.01): Phe (+42.4%), Tyr (+52.2%), Trp (+42.7%) and Lys (+66%). Concentrations of several unique metabolites differed between benign and HR RCC lesions (p<0.01): Hypoxanthine (-42%), Threonic Acid (+26%), EAP (+133%), and Glycerol-3-phosphate (+110%). HR RCC had smaller concentrations of the following metabolites versus indolent lesions (p<0.01): Betaine (-63%), Hydrouracil (-36%), N-Ac Gln (-56%), Histidine (-42%), and 2-aminoisobutyrate (-47%). CONCLUSIONS Given the prevalent metabolic rearrangements in RCC, use of urinary metabolomics represents a promising biomarker that can not only distinguish ccRCC from benign tumors, but also risk-stratify dangerous cancers from indolent ones by identifying specific metabolic profiles. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1198 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Mohit Gupta More articles by this author Hiten Patel More articles by this author Alice Semerjian More articles by this author Michael Gorin More articles by this author Michael Johnson More articles by this author Mohamad Allaf More articles by this author Phillip Pierorazio More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...
Source: The Journal of Urology
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2795636935