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中华腔镜泌尿外科杂志(电子版) ›› 2023, Vol. 17 ›› Issue (06) : 627 -632. doi: 10.3877/cma.j.issn.1674-3253.2023.06.016

临床研究

孤儿核受体HNF4α在肾透明细胞癌中的表达及意义
张圣平, 邓琼, 张颖, 张建文, 梁辉, 王铸†()   
  1. 518109　广东，深圳市龙华区人民医院泌尿外科
  • 收稿日期:2022-11-22 出版日期:2023-12-01
  • 通信作者: 王铸
  • 基金资助:
    深圳市科技计划项目(JCYJ20210324131414039); 深圳市龙华区科技创新基金(LHKJCXJCYJ202002); 深圳市龙华区医疗卫生机构科研项目(2021046)

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

Shengping Zhang, Qiong Deng, Ying Zhang, Jianwen Zhang, Hui Liang, Zhu Wang†()   

  1. Department of Urology, The People's Hospital of Longhua Shenzhen, Guangdong 518109, China
  • Received:2022-11-22 Published:2023-12-01
  • Corresponding author: Zhu Wang
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张圣平, 邓琼, 张颖, 张建文, 梁辉, 王铸. 孤儿核受体HNF4α在肾透明细胞癌中的表达及意义[J]. 中华腔镜泌尿外科杂志(电子版), 2023, 17(06): 627-632.

Shengping Zhang, Qiong Deng, Ying Zhang, Jianwen Zhang, Hui Liang, Zhu Wang. Expression and significance of the orphan nuclear receptor HNF4α in renal clear cell carcinoma[J]. Chinese Journal of Endourology(Electronic Edition), 2023, 17(06): 627-632.

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。

关键词: 肾透明细胞癌, 孤儿核受体, HNF4α, 生物信息学
Objective

To analyze the expression and significance of orphan nuclear receptor HNF4α in renal clear cell carcinoma.

Methods

The 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.

Results

HNF4α 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.

Conclusions

HNF4α 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.

Key words: Renal clear cell carcinoma, Orphan nuclear receptor, HNF4α, Bioinformatics
图1 HNF4α在肾透明细胞癌中表达谱分析注：a为UALCAN分析HNF4α mRNA相对表达量；b为UALCAN分析HNF4α蛋白相对表达量；c为TNMplot分析HNF4α mRNA相对表达量；d为TNMplot分析转移性肾透明细胞癌样本中HNF4α mRNA相对表达量
图2 HNF4α在肾透明细胞癌中的表达与肿瘤进展及预后的关系注：a为肾透明细胞癌不同分级样本中HNF4α mRNA相对表达量；b为肾透明细胞癌不同分期样本中HNF4α mRNA相对表达量；c为Kaplan-Meier Plotter分析不同HNF4α表达对预后的影响；d为UALCAN分析不同HNF4α表达对预后的影响
图3 肾透明细胞癌中与HNF4α表达呈正相关的基因分析注：a为肾透明细胞癌中与HNF4α表达呈正相关的基因热图；b为基因表达相关性分析
图4 HNF4α在肾透明细胞癌中蛋白相互作用网络分析注：a为HNF4α相互作用蛋白网络；b为HNF4α蛋白作用网络参与的主要信号通路分析
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