Abstract: Objective To analyze the expression level of phosphatidyl glutathione peroxidase 4 in prostate cancer and its significance with clinical prognosis by database mining. Methods Ualcan and GEPIA2 databases were used to analyze the expression level of GPX4 in prostate cancer. The linked Omics database was used to investigate the relationship between GPX4 and the clinicopathological stage, lymph node metastasis, Gleason score and survival prognosis of prostate cancer. The methylation level of the promoter region of GPX4 gene was assessed through the MethHC 2.0 methylation database to probe the effect of methylation on the promoter region of GPX4. The downstream molecules and related network diagrams of GPX4 gene regulation were constructed using the String database. Results Compared with normal prostate tissue, the expression level of GPX4 mRNA in prostate cancer tissue was significantly increased （P=0.000 2）. Pan-cancer expression analysis showed that GPX4 was high expression in bladder cancer, kidney cancer, urothelial cancer and other urinary system tumors. The mRNA expression level of GPX4 was correlated with the clinicopathological stage, lymph node metastasis and Gleason score of prostate cancer. Survival analysis showed that GPX4 had no correlation with the overall survival of prostate cancer patients, but patients with high GPX4 had lower recurrence-free survival. The methylation expression level of GPX4 gene DNA promoter region in prostate cancer was significantly higher than that in normal prostate epithelial tissue. The results of protein network analysis suggested that GPX4 may play a role inferroptosis, glutathione metabolism, superoxide dismutase 2, Catalase and other pathways. Conclusion The high expression of GPX4 gene in prostate cancer is an effective biomarker for predicting the occurrence and development of prostate cancer patients.

Key words: prostate cancer, glutathione peroxidase protein-4, bioinformatics

摘要： 目的 通过数据库挖掘的方法分析谷胱甘肽过氧化物酶蛋白-4（GPX4）在前列腺癌中的表达水平及其与临床预后的意义。方法 运用Ualcan、GEPIA2数据库分析GPX4在前列腺癌中的表达水平。应用linked Omics数据库探讨GPX4与前列腺癌临床病理分期、淋巴结转移情况、Gleason评分以及生存预后之间的关系。通过MethHC 2.0甲基化数据库了解GPX4基因启动子区的甲基化水平,探讨甲基化对GPX4启动子区的影响作用;利用String数据库构建GPX4基因调控的下游分子及相关网络图。结果 与正常前列腺组织相比,前列腺癌组织中GPX4转录表达水平明显升高,差异有统计学意义（P=0.0002）,泛癌表达分析显示GPX4在膀胱癌、肾癌、尿路上皮癌等泌尿系统肿瘤中也高表达。GPX4的mRNA表达水平与前列腺癌临床病理分期、淋巴结转移和Gleason评分成正相关性,生存分析显示GPX4与前列腺癌患者总生存期无相关性,但GPX4高的患者无复发生存期较低。GPX4基因DNA启动子区在前列腺癌中的甲基化表达水平较正常的前列腺上皮组织显著升高。蛋白网络分析结果提示GPX4可能在铁死亡、谷胱甘肽代谢、超氧化物歧化酶2、过氧化物酶等途径发挥作用。结论 前列腺癌中GPX4基因高表达,是预测前列腺癌患者发生、发展的有效生物标志物。

关键词: 前列腺癌, 谷胱甘肽过氧化物酶蛋白-4, 生信分析