CDH13基因在转移性肾透明细胞癌中的研究

Study on the effect of CDH13 gene on metastatic kidney clear cell carcinoma

目的:探索CDH13在转移性肾透明细胞癌(KIRC)中的异常表达及其分子机制,并分析CDH13作为KIRC预后标志物的价值。方法:分别使用TCGA和GEO数据库比较CDH13在KIRC和正常组织中的转录水平,通过实时荧光定量PCR进行验证。利用UALCAN网站分析KIRC中CDH13的蛋白表达水平和启动子区甲基化修饰水平,使用SMART网站分析不同临床分期KIRC中CDH13甲基化水平,并用MethSurv网页分析其与预后的关联。结果:与正常组织比较,CDH13 mRNA在KIRC中显著表达上调(P<0.05);但在有淋巴结、远处器官转移及Ⅲ~Ⅳ期患者中表达水平较低。CDH13的蛋白水平在转移性KIRC中,随着肿瘤的分级而不断降低。KIRC组织中CDH13启动子区甲基化水平高于正常对照样本,且肿瘤分期、分级越高,CDH13甲基化水平越高。甲基转移酶抑制剂5-aza-dC可明显恢复CDH13在KIRC细胞中的表达水平。此外,CDH13的启动子区不同cg位点的甲基化水平与患者预后密切相关,高甲基化水平越高的患者预后越差。结论:CDH13在转移性KIRC中转录和表达水平失活,并提示患者的不良预后。

Objective:To analyze the abnormal expression of CDH13 in metastatic kidney clear cell carcinoma(KIRC) and its molecular mechanism,and to analyze the value of CDH13 as a prognostic marker of KIRC.Methods:The transcription level of CDH13 in KIRC tissues and normal tissues were compared using TCGA and GEO databases,and verified by real-time fluorescence quantitative PCR.Methylation of CDH13 protein and promoter region in KIRC was analyzed using the UALCAN website.Methylation expression in KIRC and different tumor stages were analyzed using SMART website,and its association with prognosis was analyzed using MethSurv website.Results:The expression of CDH13 mRNA was significantly up-regulated in KIRC tissues,but it was decreased in patients with lymph node metastasis,distant organ metastasis,and in stages Ⅲ-Ⅳ(P<0.05).The protein level of CDH13 in metastatic KIRC decreases with tumor grade.The methylation level of the CDH13 promoter region in KIRC tissues was also higher than that in normal control samples and was remarkably elevated with the tumor stage and grade.The methyltransferase inhibitor 5-aza-dC significantly restored the expression level of CDH13 in KIRC cells.In addition,methylation levels at different CG sites in the promoter region of CDH13 were closely related to the prognosis of patients,and patients with hypermethylation had a worse prognosis.Conclusion:The transcription and expression levels of CDH13 are inactivated in metastatic KIRC,and it indicates a poor prognosis of patients.