Renal Cell Carcinoma: A Study through NMR-Based Metabolomics Combined with Transcriptomics

Abstract

Renal cell carcinoma (RCC) is a heterogeneous cancer often showing late symptoms. Until now, some candidate protein markers have been proposed for its diagnosis. Metabolomics approaches have been applied, predominantly using Mass Spectrometry (MS), while Nuclear Magnetic Resonance (NMR)-based studies remain limited. There is no study about RCC integrating NMR-based metabolomics with transcriptomics. In this work, ¹H-NMR spectroscopy combined with multivariate statistics was applied on urine samples, collected from 40 patients with clear cell RCC (ccRCC) before nephrectomy and 29 healthy controls; nine out of 40 patients also provided samples one-month after nephrectomy. We observed increases of creatine, alanine, lactate and pyruvate, and decreases of hippurate, citrate, and betaine in all ccRCC patients. A network analysis connected most of these metabolites with glomerular injury, renal inflammation and renal necrosis/cell death. Interestingly, intersecting metabolites with transcriptomic data from CD133+/CD24+ tumoral renal stem cells isolated from ccRCC patients, we found that both genes and metabolites differentially regulated in ccRCC patients belonged to HIF-α signaling, methionine and choline degradation, and acetyl-CoA biosynthesis. Moreover, when comparing urinary metabolome of ccRCC patients after nephrectomy, some processes, such as the glomerular injury, renal hypertrophy, renal necrosis/cell death and renal proliferation, were no more represented.