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, sIL-6R) in RAGE and IL-6 signaling, the modulatory effect of TK-1and TuM2-PK 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, ADMA, SDMA, and thiol-disulfide equilibrium for early diagnosis of ccRCC. Moreover, they could be considered a specific disease PTM signature which underlines the transition from early to advanced stages in this neoplasia, and of a therapeutic target in kidney oncogenesis.

中文翻译：

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透明细胞肾细胞癌的翻译后修饰模式


翻译后修饰是动态的酶介导过程，在时间和空间上受到调节，与癌症的发展相关。我们的目的是评估翻译后修饰在透明细胞肾细胞癌发病机制中的重要性。作者开展了一项为期三年的前瞻性观察性研究，纳入了 55 名局限性肾细胞癌患者和 30 名健康受试者。在本研究中，评估了受评估受试者的血清中的糖基化、硝化和羰基化、硫醇-二硫化物稳态、甲基化、磷酸化和蛋白水解裂解。我们的结果显示了早期 ccRCC 的一些特征：细胞因子的高产量、底物高唾液酸化、诱导的亚硝化和羰基应激、精氨酸高甲基化、硫醇/二硫键稳态 (TDH) 改变、可溶性受体 (sRAGE、sIL-6R) 在 RAGE 中的调节作用IL-6 信号传导、TK-1 和 TuM2-PK 在控制肿瘤细胞中磷酸代谢物水平方面的调节作用。这些数据可能是开发一组生物标志物的初始点，例如用于 ccRCC 早期诊断的总唾液酸、类粘蛋白、硝基酪氨酸、羰基代谢物、ADMA、SDMA 和硫醇二硫化物平衡。此外，它们可以被认为是一种特定的疾病 PTM 特征，强调了这种肿瘤从早期到晚期的转变，也是肾脏肿瘤发生的治疗靶点。