Quantitative global proteome and phosphorylome analyses reveal potential biomarkers in kidney cancer.

Abstract

Currently, high-throughput quantitative proteomic and transcriptomic approaches have been widely used for exploring the molecular mechanisms and acquiring biomarkers for cancers. Our study aimed to illuminate the multi-dimensional molecular mechanisms underlying renal cell carcinoma (RCC) via investigating the quantitative global proteome and the profile of phosphorylation. A total of 5,428 proteins and 8,632 phosphorylation sites were quantified in RCC tissues, with 709 proteins and 649 phosphorylation sites found to be altered in expression compared with the matched adjacent non-tumor tissues. These differentially expressed proteins were mainly involved in metabolic process terms involving the glycolysis pathway, oxidative phosphorylation and fatty acid metabolism which have been considered to be a potential mechanism of RCC progression. Moreover, phosphorylation analysis indicated that these upregulated phosphorylated proteins are implicated in the glucagon signaling pathway and cholesterol metabolism, while the downregulated phosphorylated proteins were found to be predominantly involved in glycolysis, the pentose phosphate pathway, carbon metabolism and biosynthesis of amino acids. In addition, several new candidate proteins, CD14, MPO, NCF2, SOD2, PARP1, were found to be upregulated and MUT, ACADM, PCK1 were downregulated in RCC. These proteins may be recognized as new biomarkers for RCC. These findings could broaden our insight into the underlying molecular mechanisms of RCC and identify candidate biomarkers for the treatment of RCC.