基于数据挖掘分析GPX4在胃癌中的表达及临床意义

目的探索谷胱甘肽过氧化物酶4（GPX4）在胃癌中的表达及临床意义。 方法检索收集Oncomine和基因表达谱动态分析（GEPIA）数据库中GPX4 mRNA在常见肿瘤中的表达情况，并分析其在胃癌中的表达及与患者预后的关系。利用cBioPortal在线分析癌症基因图谱（TCGA）数据库中1178例胃癌样本中的RNA测序数据，分析GPX4基因的突变情况及其与预后的关系。利用String数据库预测与GPX4相互作用的蛋白。 结果Oncomine数据库中共收集了459项关于GPX4基因在常见肿瘤及正常组织中的对照研究，其中22项表达差异具有统计学意义（P<0.0001）。GEPIA数据库分析结果显示GPX4 mRNA在胃癌组织中高表达（P<0.01），且与不良的总体生存期及无进展生存期明显相关（P<0.05），但与胃癌的TNM分期无明显相关性（P>0.05）。对TCGA数据库的RNA测序结果分析发现，在1178例胃癌样本中有25例发生GPX4基因变异，总变异率为2.1%。Kaplan-Meier生存曲线分析显示，GPX4基因变异与否，与总体生存期及无进展生存期无明显相关性（P>0.05）。GSR、GSS、GGT1/5/6/7，GSTO2，GRSF1，SOD1/2等蛋白与GPX4有明显的相互作用（P=1.94×10^-7）。 结论利用多种肿瘤基因数据库分析表明，GPX4基因在胃癌组织中变异率低，其mRNA水平高表达与患者不良预后相关，为进一步探究GPX4在胃癌的发生发展中的作用提供了重要理论依据。

Clinical significance of expression of GPX4 in gastric cancer

ObjectiveTo investigate the expression of glutathione peroxidase 4 (GPX4) in gastric cancer and to analyze its clinical significance. MethodsThe expression of GPX4 mRNA in common tumors was analyzed based on Oncomine and Gene Expression Profiling Interactive Analysis (GEPIA) databases, and its expression in gastric cancer tissues and relationship with prognosis were also analyzed. The RNA sequencing data of 1178 gastric cancer samples in The Cancer Geneome Atlas (TCGA) database were obtained via cBioPortal to analyze the mutations of the GPX4 gene and their relationship with prognosis. Proteins interacting with GPX4 were predicted using the String database. ResultsA total of 459 studies on GPX4 gene in common tumors and normal tissues were collected from the Oncomine database, 22 of which showed significantly differential GPX4 expression (P<0.0001). GEPIA database analysis showed that GPX4 mRNA was highly expressed in gastric cancer tissues (P<0.01), which was significantly associated with poor overall survival and progression-free survival (P<0.05), but had no significant correlation with TNM stage of gastric cancer (P>0.05). Analysis of RNA sequencing results in the TCGA database revealed that GPX4 gene mutations occurred in 25 of 1178 gastric cancer samples, with a total mutation rate of 2.1%. Kaplan-Meier survival curve analysis showed that there was no significant correlation between GPX4 gene mutation and OS or PFS (P>0.05). Proteins such as GSR, GSS, GGT1/5/6/7, GSTO2, GRSF1, and SOD1/2 had obvious interactions with GPX4 (P=1.94×10^-7). ConclusionThe analysis of multiple tumor gene databases shows that the GPX4 gene has a low mutation rate in gastric cancer tissues, and its high mRNA expression is associated with a poor prognosis. Our findings provide an important theoretical basis for further exploration of the role for GPX4 in the development of gastric cancer.