透明细胞肾细胞癌的综合糖蛋白质组学特征分析。
Integrated glycoproteomic characterization of clear cell renal cell carcinoma.
机构信息
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
出版信息
Cell Rep. 2023 May 30;42(5):112409. doi: 10.1016/j.celrep.2023.112409. Epub 2023 Apr 18.
Clear cell renal cell carcinoma (ccRCC), a common form of RCC, is responsible for the high mortality rate of kidney cancer. Dysregulations of glycoproteins have been shown to associate with ccRCC. However, the molecular mechanism has not been well characterized. Here, a comprehensive glycoproteomic analysis is conducted using 103 tumors and 80 paired normal adjacent tissues. Altered glycosylation enzymes and corresponding protein glycosylation are observed, while two of the major ccRCC mutations, BAP1 and PBRM1, show distinct glycosylation profiles. Additionally, inter-tumor heterogeneity and cross-correlation between glycosylation and phosphorylation are observed. The relation of glycoproteomic features to genomic, transcriptomic, proteomic, and phosphoproteomic changes shows the role of glycosylation in ccRCC development with potential for therapeutic interventions. This study reports a large-scale tandem mass tag (TMT)-based quantitative glycoproteomic analysis of ccRCC that can serve as a valuable resource for the community.
透明细胞肾细胞癌（ccRCC）是 RCC 的常见形式，是导致肾癌高死亡率的主要原因。糖蛋白的失调已被证明与 ccRCC 相关。然而，其分子机制尚未得到很好的描述。在这里，使用 103 个肿瘤和 80 对配对的正常相邻组织进行了全面的糖蛋白质组学分析。观察到糖基化酶和相应的蛋白质糖基化发生改变，而 ccRCC 的两个主要突变基因 BAP1 和 PBRM1 显示出不同的糖基化谱。此外，还观察到肿瘤内异质性和糖基化与磷酸化之间的交叉相关性。糖蛋白质组学特征与基因组、转录组、蛋白质组和磷酸化蛋白质组变化的关系表明了糖基化在 ccRCC 发展中的作用，具有潜在的治疗干预作用。本研究报告了 ccRCC 的基于串联质量标签（TMT）的大规模定量糖蛋白质组学分析，可为该领域提供有价值的资源。
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