Patients with ClearCode34-identified molecular subtypes of clear cell renal cell carcinoma represent unique populations with distinct comorbidities

• Published in: Urologic oncology Vol. 34; no. 3; pp. 122.e1 - 122.e7
• Main Authors: Haake, Scott M., M.D, Brooks, Samira A., Ph.D, Welsh, Eric, Ph.D, Fulp, William J., M.S, Chen, Dung-Tsa, Ph.D, Dhillon, Jasreman, M.D, Haura, Eric, M.D, Sexton, Wade, M.D, Spiess, Philippe E., M.D, Pow-Sang, Julio, M.D, Rathmell, W. Kimryn, M.D., Ph.D, Fishman, Mayer, M.D., Ph.D
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2016
• Subjects: Aged; Biomarkers, Tumor - genetics; Carcinoma, Renal Cell - classification; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - secondary; Clear cell renal cell carcinoma; ClearCode34; Comorbidity; Diabetes mellitus; Female; Follow-Up Studies; Humans; Kidney Neoplasms - classification; Kidney Neoplasms - genetics; Kidney Neoplasms - pathology; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local - classification; Neoplasm Recurrence, Local - genetics; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Obesity; Prognosis; Retrospective Studies; Survival Rate; Transcriptome; Urology; Obesity; Clear cell renal cell carcinoma; ClearCode34; Diabetes mellitus
• ISSN: 1078-1439; 1873-2496
• DOI: 10.1016/j.urolonc.2015.09.015

Abstract Purpose The 34-gene classifier, ClearCode34, identifies prognostically distinct molecular subtypes of clear cell renal cell carcinoma (ccRCC) termed clear cell A (ccA) and clear cell B (ccB). The primary objective of this study was to describe clinical characteristics and comorbidities of relevance in patients stratified by ClearCode34. Patients and methods In this retrospective analysis, 282 patients from Moffitt Cancer Center with ccRCC with gene expression analyses of the primary tumor were identified and ClearCode34 was applied to identify tumors as ccA or ccB. The medical record and institutional databases were queried to define patient characteristics, comorbidities, and outcomes. Results We validated in this external cohort the superior overall survival, cancer-specific survival, and recurrence-free survival of ccA patients relative to ccB patients ( P <0.001). Addressing other clinical characteristics, the ccA patients were more likely to be obese (48% vs. 34%, P = 0.021) and diabetic (26% vs. 13%, P = 0.035). The ccA patients also trended toward having been more frequent users of angiotensin system inhibitors (71% vs. 52%, P = 0.055). In multivariate analyses, ccB status is independently associated with inferior cancer-specific survival (hazard ratio = 3.26, 95% confidence interval: 1.84–5.79) and overall survival (hazard ratio = 2.50, 95% confidence interval: 1.53–4.08). Conclusions ClearCode34, after considering distinct patterns of comorbidities in each molecular subtype, remains a strong prognostic tool in patients with ccRCC. Obesity and diabetes mellitus emerged as factors that may influence ccRCC phenotypes and further studies investigating the effect of these metabolic conditions functionally onto tumor biology are warranted. Additionally, use of angiotensin system inhibitors could be studied in the context of ccRCC molecular classification in future studies to better understand its effect on ccRCC outcomes.