Posttranslational Modifications Pattern in Clear Cell Renal Cell Carcinoma

Abstract

Posttranslational modifications are dynamic enzymatic-mediated processes, regulated in time and space, associated with cancer development. We aimed to evaluate the significance of posttranslational modifications in the pathogenesis of clear cell renal cell carcinoma. The authors developed a prospective, observational study during a period of three years and included 55 patients with localized renal cell carcinoma and 30 heathy subjects. Glycosylation, nitration and carbonylation, thiol-disulfide homeostasis, methylation, phosphorylation and proteolytic cleavage were evaluated in the serum of the evaluated subjects in the present study. Our results showed some characteristics for early ccRCC: high production of cytokines, substrate hypersialylation, induced nitrosative and carbonylic stress, arginine hypermethylation, thiol/disulfide homeostasis (TDH) alteration, the regulatory role of soluble receptors (sRAGE—soluble receptor for advanced glycation end products, sIL-6R—soluble receptor for Interleukin 6) in RAGE and IL-6 signaling, the modulatory effect of TK1—thymidine kinase 1 and TuM2-PK—tumoral pyruvate-kinase 2 in controlling the level of phosphometabolites in neoplastic cells. These data could be the initial point for development of a panel of biomarkers such as total sialic acid, orosomucoids, nitrotyrosine, carbonylic metabolites, Asymmetric Dimethylarginines (ADMA), Symmetric Dimethylarginines (SDMA), and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease posttranslational modification signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis.