Renal cell carcinoma (RCC) is a heterogeneous malignancy which often develops and progresses asymptomatically. Benign oncocytomas are morphologically similar to malignant chromophobe RCC and distinguishing between these two forms on cross-sectional imaging remains a challenge. Therefore, RCC-specific biomarkers are urgently required for accurate and non-invasive, pre-surgical diagnosis of benign lesions. We have previously shown that dysregulation in glycolytic and tricarboxylic acid cycle intermediates can distinguish benign lesions from RCC in a stage-specific manner. In this study, preoperative fasting urine samples from patients with renal masses were assessed by ¹H nuclear magnetic resonance (NMR). Significant alterations in levels of tricarboxylic acid cycle intermediates, carnitines and its derivatives were detected in RCC relative to benign masses and in oncocytomas vs. chromophobe RCC. Orthogonal Partial Least Square Discriminant Analysis plots confirmed stage discrimination between benign vs. pT1 (R2 = 0.42, Q2 = 0.27) and benign vs. pT3 (R2 = 0.48, Q2 = 0.32) and showed separation for oncocytomas vs. chromophobe RCC (R2 = 0.81, Q2 = 0.57) and oncocytomas vs. clear cell RCC (R2 = 0.32, Q2 = 0.20). This study validates our previously described metabolic profile distinguishing benign tumors from RCC and presents a novel metabolic signature for oncocytomas which may be exploited for diagnosis before cross-sectional imaging.

Metabolites. 2019 Jul 24*** epublish ***

Oluyemi S Falegan, Shanna A Arnold Egloff, Andries Zijlstra, M Eric Hyndman, Hans J Vogel

Department of Biological Sciences, University of Calgary, Calgary, AB T2N 4V8, Canada., Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, TN 37232, USA., Department of Surgery, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada., Department of Biological Sciences, University of Calgary, Calgary, AB T2N 4V8, Canada. .