SKP1、SKP2对肾癌预后的预测作用分析  

Association of SKP1 and SKP2 expression with the prognosis of renal cell carcinomas

作　　者：杨伟芳[1] 杨海华[1] 冉刚[1] 皮文虎 王学全 YANG Weifang;YANG Haihua;RAN Gang;PI Wenhu;WANG Xuequan(Department of Radiation Oncology,Taizhou Hospital of Zhejiang Province,Taizhou 317000,China)

机构地区：[1]浙江省台州医院放疗科,317000

出　　处：《浙江医学》2022年第19期2075-2080,I0005,I0006,共8页Zhejiang Medical Journal

基　　金：浙江省卫生健康科技计划项目(2022KY1382);台州市科技计划项目(1901ky07)。

摘　　要：目的分析S期激酶相关蛋白1(SKP1)和S期激酶相关蛋白2(SKP2)表达水平对肾透明细胞癌、肾嫌色细胞癌、肾乳头状细胞癌这3种肾癌患者预后的预测作用。方法使用TCGA数据库中肾透明细胞癌、肾嫌色细胞癌、肾乳头状细胞癌样本进行SKP1和SKP2表达水平及其甲基化与预后相关性分析、不同表达水平间基因突变情况分析。采用Metascape数据库分析SKP2在这3种肾癌中共表达基因功能富集情况及蛋白质相互作用情况。结果与正常组织比较,SKP1表达水平在这3种肾癌中均显著降低,SKP2在肾透明细胞癌和肾乳头状细胞癌中显著升高。在这3种肾癌中SKP2高表达者预后均较差,AUC值和一致性指数提示预测准确性稳定。肾癌中多个甲基化位点与SKP1或SKP2表达水平及预后显著相关。肾透明细胞癌中SKP1和SKP2突变占14%。KMT2C、HERC2、PRKDC、SETD2和HMCN1基因突变与SKP1或SKP2表达水平高低相关。肾癌中SKP2共表达基因富集部分与免疫应答调节相关。结论SKP2及其甲基化可以预测肾癌预后。肾癌中SKP1、SKP2表达高低与KMT2C、HERC2、PRKDC、SETD2和HMCN1等基因突变相关,并受多种甲基化位点影响。Objective To analyze the relationship of the expression levels of S-phase kinase-associated protein 1(SKP1)and S-phase kinase-associated protein 2(SKP2)with the prognosis of renal cell carcinoma.Methods The SKP1 and SKP2 expression levels in kidney clear cell carcinoma(KIRC),kidney chromophobe cell carcinoma(KICH)and kidney papillary cell carcinoma(KIRP)and their relationship with methylation,prognosis,and gene mutations was analyzed using TCGA database.The gene function enrichment and protein interaction of SKP2 in renal cell carcinomas were analyzed by using metascape database.Results Compared with normal tissues,the expression levels of SKP1 were decreased in all three types of renal cell carcinomas,and SKP2 were increased in KIRC and KIRP.The patients with high expression levels of SKP2 had poorer prognosis in all the three kinds of renal cell carcinoma(P<0.05).AUC value and consistency index suggested that the prediction accuracy was stable.The expression levels of SKP1 or SKP2 and the prognosis of renal cell carcinoma were significantly correlated with multiple methylation sites.SKP1 and SKP2 mutations accounted for 14%of renal clear cell carcinoma.Mutations in KMT2C,HERC2,PRKDC,SETD2 and HMCN1 genes were associated with the expression levels of SKP1 or SKP2 in renal cell carcinoma.Enrichment analysis of SKP2 co-expressed genes in renal cell carcinoma showed that some of its functions were related to the regulation of immune response.Conclusion SKP2 and its methylation may predict the prognosis of patients with renal cell carcinoma.The expression levels of SKP1 or SKP2 in kidney cancer are related to gene mutations such as KMT2C,HERC2,PRKDC,SETD2 and HMCN1;they are also affected by a variety of methylation sites.

关 键 词：肾癌 S期激酶相关蛋白1 S期激酶相关蛋白2 预后 

分 类 号：R737.11[医药卫生—肿瘤]