Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310016, P.R. China.
Oncol Rep. 2021 Nov;46(5). doi: 10.3892/or.2021.8188. Epub 2021 Sep 16.
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.
目前,高通量定量蛋白质组学和转录组学方法已广泛用于探索癌症的分子机制和获取生物标志物。我们的研究旨在通过研究定量的全蛋白质组和磷酸化谱来阐明肾细胞癌 (RCC) 的多维分子机制。在 RCC 组织中定量了 5428 种蛋白质和 8632 个磷酸化位点,与匹配的相邻非肿瘤组织相比,发现 709 种蛋白质和 649 个磷酸化位点的表达发生了改变。这些差异表达的蛋白质主要涉及涉及糖酵解途径、氧化磷酸化和脂肪酸代谢的代谢过程术语,这些已被认为是 RCC 进展的潜在机制。此外,磷酸化分析表明,这些上调的磷酸化蛋白与胰高血糖素信号通路和胆固醇代谢有关,而下调的磷酸化蛋白主要涉及糖酵解、戊糖磷酸途径、碳代谢和氨基酸生物合成。此外,还发现了几种新的候选蛋白,如 CD14、MPO、NCF2、SOD2、PARP1 在 RCC 中上调,而 MUT、ACADM、PCK1 下调。这些蛋白可能被认为是 RCC 的新生物标志物。这些发现可以拓宽我们对 RCC 潜在分子机制的认识,并为 RCC 的治疗确定候选生物标志物。