肾透明细胞癌非标记定量蛋白质组学及磷酸化修饰组学分析  

Label-free quantitative proteomics and phosphoproteomics analysis of clear cell renal cell carcinoma

作　　者：古丽乃再尔·阿卜杜赛麦提 段霜霜 柳惠斌[2] Gulinaizaier Abudusaimaiti;DUAN Shuangshuang;LIU Huibin(Department of Pharmacy,Xinjiang Medical University,Xinjiang Urumqi 830011,China;Clinical Trials Center,Affiliated Tumor Hospital of Xinjiang Medical University,Xinjiang Urumqi 830011,China)

机构地区：[1]新疆医科大学药学院,新疆乌鲁木齐830011 [2]新疆医科大学附属肿瘤医院临床试验中心,新疆乌鲁木齐830011

出　　处：《现代肿瘤医学》2024年第4期617-622,共6页Journal of Modern Oncology

基　　金：新疆维吾尔自治区科技支疆项目计划(编号:2022E02131)。

摘　　要：目的:应用非标记定量蛋白质组学分析技术,筛选与肾透明细胞癌(clear cell renal cell carcinoma,ccRCC)发病机制相关的蛋白质,发现ccRCC新的诊疗靶点。方法:选取2017年01月至2020年12月在新疆医科大学附属肿瘤医院泌尿外科手术治疗并经术后病理证实的ccRCC及癌旁组织样本30例,利用非标记定量蛋白质组学及磷酸化修饰组学技术,分析差异表达的蛋白质及磷酸化修饰位点。生物信息学分析关键蛋白激酶、磷酸化位点以及信号通路。结果:组学联合分析策略共鉴定到2552个差异总蛋白、3024个差异表达的磷酸化位点及与之对应的1572个磷酸化蛋白。功能富集和聚类分析表明差异磷酸化蛋白主要涉及ErbB信号传导途径、VEGF信号传导通路和细胞黏附通路等重要信号通路,其中PDHK1、NDR1、NDR2及MST1可能成为新型候选标志物和药物作用靶点。结论:ccRCC与癌旁正常组织的总蛋白及磷酸化蛋白表达水平存在显著差异,有望成为肾透明细胞癌精准诊疗潜在的研究应用方向。Objective:To utilize phosphoproteomics and proteomics combined analysis techniques to identify differentially expressed proteins related to the pathogenesis of clear cell renal cell carcinoma(ccRCC)and discover novel diagnosis and treatment targets for ccRCC.Methods:We selected cancer tissue and adjacent tissue samples from 30 ccRCC patients who underwent urological surgery at the Affiliated Tumor Hospital of Xinjiang Medical University between January 2017 to December 2020.Label-free quantitative proteomics and phosphorylation modification techniques were used to analyze the differentially expressed proteins and phosphorylation modification sites.Bioinformatics analyzed the key protein kinases,phosphorylation sites and signaling pathways.Results:A total of 2552 differentially expressed total proteins,3024 differentially expressed phosphorylation sites and 1572 phosphorylated proteins corresponding to them were identified by the combined histological analysis strategy.Functional enrichment and clustering analysis showed that the differentially phosphorylated proteins were mainly involved in important signaling pathways such as ErbB signaling pathway,VEGF signaling pathway,and cell adhesion pathway,among which PDHK1,NDR1,NDR2 and MST1 might become novel candidate markers and drug targets.Conclusion:The expression levels of total protein and phosphorylated protein in ccRCC and normal tissues next to cancer are significantly different,which is expected to be a potential research application direction for precision diagnosis and treatment of ccRCC.

关 键 词：蛋白质组学 磷酸化蛋白质组学 肾透明细胞癌 生物信息学分析 

分 类 号：R737.11[医药卫生—肿瘤]