摘要： 目的 研究乳头状肾细胞癌（PRCC）患者与正常人的差异基因，并探讨其与患者总体生存期（OS）的关系。方法 从癌症基因组图谱（TCGA）数据库中下载PRCC患者的基因表达谱数据和临床信息，筛选差异表达基因。通过Cox风险回归分析、Kaplan-Meier生存曲线和受试者操作特征（ROC）曲线分析，鉴定与OS相关的独立预后标志物。采用MTT方法检测细胞增殖水平。结果 通过对正常人和PRCC患者的基因进行差异分析，筛选出74个差异表达基因（log FC>5，FDR<0.05）。单因素Cox风险回归分析发现，16个基因与患者生存相关。Kaplan-Meier生存曲线和ROC曲线证实，只有TERT基因可以准确预测患者预后（曲线下面积=0.713）。TERT高表达患者的OS较低表达患者明显缩短（P=0.009）。对临床因素进行单因素、多因素Cox风险回归分析，结果提示，TERT （多因素，P=0.005）和N分期（多因素，P<0.001）是PRCC患者OS的独立预后因素，TERT高表达的PRCC患者具有高死亡风险。转染cDNA-TERT至PRCC细胞后，与未转染组比较，细胞增殖活性增加（P<0.05）。结论 TERT基因高表达与PRCC患者预后不良相关，可作为PRCC患者OS的独立预后因素和潜在的治疗新靶点。

TERT基因在乳头状肾细胞癌中的独立预后作用

刘殿勇¹, 张帅¹, 许亚坤¹, 高莉娟¹, 杨进益², 魏伟²

1. 大连医科大学附属大连市儿童医院泌尿外科, 辽宁 大连 116012;
2. 大连医科大学附属大连市友谊医院泌尿外科, 辽宁 大连 116100

收稿日期:2021-01-08出版日期:2021-07-30发布日期:2021-06-24
通讯作者:魏伟E-mail:doctorwei@126.com
作者简介:刘殿勇(1980-),男,副主任医师,硕士.
基金资助:辽宁省科学技术计划（201602218）


关键词: 乳头状肾细胞癌, 总体生存期, 预后标志物, 治疗靶点
Abstract: Objective To identify genes differentially expressed between normal subjects and patients with papillary renal cell carcinoma (PRCC), and assess the relationship between these genes and overall survival (OS) of patients. Methods Relevant data from PRCC patients were downloaded from the Cancer Genome Atlas (TCGA) database to screen for differentially expressed genes. Cox hazard regression analysis,a Kaplan-Meier survival curve,and a receiver operating characteristic (ROC) curve were used to identify independent prognostic markers associated with OS. Cell proliferation was monitored in vitro via MTT assay. Results Seventy-four differentially expressed genes (log FC>5,FDR<0.05) were identified that displayed differential expression between normal subjects and PRCC patients. Cox hazard regression analysis showed that 16 genes were associated with survival. The Kaplan-Meier survival and ROC curves confirmed that only the TERT gene could accurately predict patient prognosis (AUC=0.713). The OS was significantly shortened in patients with high TERT expression compared with those with low TERT expression (P=0.009). Univariate and multivariate Cox hazard regression analyses of clinical factors showed that TERT (multivariate:P=0.005) and N stage (multivariate:P=0.011) were independent prognostic factors of OS in PRCC patients. PRCC patients with high TERT expression were at higher risk of death. Moreover,TERT overexpression in a kidney renal papillary cell line increased proliferation compared with the untransfected group (P<0.005). Conclusion High expression of the TERT gene is associated with poor prognosis,can be used as an independent prognostic factor,and represents a potential new therapeutic target for increasing OS in PRCC patients.
Key words: papillary renal cell carcinoma, overall survival, prognostic biomarker, therapeutic target
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