孤儿核受体HNF4α在肾透明细胞癌中的表达及意义

Expression and significance of the orphan nuclear receptor HNF4α in renal clear cell carcinoma

目的基于数据挖掘分析孤儿核受体HNF4α在肾透明细胞癌(ccRCC)中的表达及意义。方法UALCAN分析HNF4α在肾透明细胞癌组织中的表达及其与患者总生存率的关系,分析与HNF4α表达具有相关性的基因群。TNMplot分析HNF4α基因mRNA在肿瘤、正常和转移组织中的表达。Kaplan-Meier Plotter分析HNF4α表达与肿瘤生存率的关系。STRING分析HNF4α蛋白质-蛋白质相互作用网络。结果HNF4α在肾透明细胞癌细胞中显著下调(P=0.002);在转移性肾透明细胞癌中表达水平进一步下调(P<0.001);HNF4α表达水平在肿瘤分级4级显著低于1级(P=0.007),在4级显著低于3级(P<0.001)。HNF4α表达水平与肿瘤预后呈负相关(P=0.017)。HNF4α低表达组总生存率显著低于高表达组(P<0.001)。Pearson相关系数>0.5的HNF4α表达正相关的基因有27个,其中ERBB3、CUBN、HNF1A、CES2与HNF4α表达相关系数最高。HNF4α与HNF1A、EP300、LEF1、SMAD3、SMAD4、NCOA1、HIF1A、FOXO1以及PPARGC1A均存在相互作用,其相互作用网络节点为11,蛋白-蛋白相互作用富集P值为3.44e-08。结论HNF4α在肾透明细胞癌中表达显著下调,并与肿瘤预后呈负相关,HNF4α及其相互作用关键因子可能在肾透明细胞癌发生、发展过程中扮演重要角色,具体作用及分子机制需进一步研究。

ObjectiveTo analyze the expression and significance of orphan nuclear receptor HNF4α in renal clear cell carcinoma.MethodsThe expression pattern of HNF4α in renal clear cell carcinoma and its related overall survival was analyzed by UALCAN. The expression of HNF4α mRNA in tumor, normal and metastatic tissues of renal clear cell carcinoma was analyzed by TNMplot. The prognostic significance of HNF4α in renal clear cell carcinoma was evaluated in Kaplan-Meier plotter online database. STRING analysis was used to analyze the HNF4α related protein-protein interaction networks.ResultsHNF4α was significantly down regulated in renal clear cell carcinoma as compared to its normal control (P=0.002). The expression level of HNF4α was lower in metastatic renal clear cell carcinoma than that in primary tumor tissues (P<0.001). The expression level of HNF4α in stage 4 was significantly lower than that in stage 1 (P=0.007), and in grade 4 was significantly lower than that in grade 3 (P<0.001). The expression level of HNF4α was positively correlated with tumor prognosis (P=0.017). The overall survival rate of HNF4α-low expressed group was significantly lower than that of high expression group (P<0.001). There were 27 genes positively correlated with the expression of HNF4α with Pearson correlation coefficient greater than 0.5, including ERBB3, CUBN, HNF1A and CES2. There were interactions between HNF4α and HNF1A, EP300, LEF1, SMAD3, SMAD4, NCOA1, HIF1A, FOXO1 and PPARGC1A. The interaction network node is 11, and the PPI enrichment P value is 3.44e-08.ConclusionsHNF4α is significantly down regulated in renal clear cell carcinoma and negatively correlated with tumor prognosis. HNF4α and its related interaction factors may play important roles in the renal clear cell carcinoma. However, the role and mechanism of HNF4α in renal clear cell carcinoma need to be further studied.