抑癌基因TCF21启动子甲基化在肾癌诊断及预后中的意义

Significance of Tumor Suppressor Gene TCF21 Promoter Methylation for Diagnosis and Prognosis of Renal Cell Carcinoma

目的探讨TCF21启动子甲基化在肾癌诊断与预后中的意义。方法使用焦磷酸测序仪对样本的TCF21基因启动子甲基化水平进行定量检测,并进行统计学分析。结果肾癌组织及尿液中TCF21基因甲基化水平明显升高(P=0.000,P=0.0 0 0)。肾癌组织T C F 2 1基因甲基化水平与年龄(P=0.003)、吸烟史(P=0.018)、Fuhrman分级(P=0.046)及临床分期(P=0.048)有关,TCF21甲基化水平与年龄(r=0.403、P=0.002)、吸烟史(r=0.321、P=0.017)和Fuhrman分级(r=0271、P=0.045)呈正相关。肾癌尿液中TCF21甲基化水平与肿瘤大小(P=0.000)、Fuhrman分级(P=0.013)及临床分期(P=0.020)有关,TCF21甲基化水平与肿瘤大小(r=0.662、P=0.000)、Fuhrman分级(r=0.662、P=0.010)和临床分期(r=0.662、P=0.017)呈正相关。TCF21高甲基化组(>35.42%)与TCF21低甲基化组(≤35.42%)患者术后生存率和总生存率差异有统计学意义(P=0.000,P=0.000)。肾癌组织中TCF21甲基化水平诊断肾癌的ROC曲线下面积高于尿液样本,差异具有统计学意义(P=0.004)。结论 TCF21与肾细胞癌的发生、发展及预后有关。联合检测肾细胞癌组织标本和尿液标本可作为诊断肾癌及判断预后等生物学行为的重要指标。

Objective To investigate the clinical significance of promoter methylation of TCF21 for the diagnosis and prognosis of renal cell carcinoma（RCC）. Methods Pyrosequencing technology was applied for quantitative detection of methylation level of TCF21 in the RCC and urine specimens. Statistics analysis was made after the detection. Results The methylation levels of TCF21 in RCC tissues and urine specimens were both increased（P=0.000, P=0.000）. In RCC tissues, TCF21 methylation levels were closely related to age（P=0.003）, smoking history（P=0.018）, Fuhrman grade（P=0.046） and clinical stage（P=0.048）. Correlation analysis found that there was a positively linear correlation between TCF21 methylation levels and age（r=0.403, P=0.002）, smoking history（r=0.321, P=0.017） and Fuhrman grade（r=0.271, P=0.045） in RCC. In urine specimens, TCF21 methylation levels were closely related to tumor size（P=0.000）, Fuhrman grade（P=0.013） and clinical stage（P=0.020）. Correlation analysis found that there was a positively linear correlation between TCF21 methylation levels and tumor size（r=0.662, P=0.000） Fuhrman grade（r=0.441, P=0.010）and clinical stage（r=0.411, P=0.017） in RCC urine. And we found there were significant differences in postoperative and overall survival rates between high TCF21 methylation level（35.42%） group and low TCF21 methylation level（≤35.42%） group（P=0.000, P=0.000）. The area under ROC curve of TCF21 methylation levels in RCC tissues was higher than urine specimens（P=0.004）. Conclusion TCF21 is associated with the occurrence, development and prognosis of RCC. The joint detection of RCC tissues specimens and RCC urine specimens may be used as important indexes for the diagnosis, prognosis and other biological behaviors of RCC.