摘要
目的 探讨谷胱甘肽还原酶(Glutathione reductase,GSR)对结肠恶性肿瘤代谢的影响及其对结肠癌患者的预后价值.方法 通过蛋白组学差异分析获得结肠癌组织和正常结肠上皮组织的差异蛋白,并通过富集分析和蛋白-蛋白相互作用网络(PPI)分析鉴定代谢通路中的关键蛋白,进行生存分析和临床信息相关性分析.收集120例结肠癌患者手术病理标本制作组织微阵列芯片,进行免疫组织化学染色.结果 蛋白组学差异分析共鉴定出1 209个差异表达蛋白.KEGG富集分析显示,差异蛋白显著富集于代谢通路,共富集144个蛋白.PPI分析显示ADH1A、ADH1B、ADH1C、ADH5、ALDH18A1、ALDH3A1、GSTA1、GSTA2、HPGDS、GSR 是结肠癌差异蛋白代谢通路中的关键蛋白.GEPIA2生存分析显示,GSR影响结肠癌患者的总生存期(P=0.0 017,HR=0.45).UALCAN数据库分析显示,GSR高表达的结肠癌患者N分期、总分期更低,TP53突变率更低.组织微阵列芯片免疫组化结果显示GSR在正常结肠上皮组织中表达水平最高,在合并肝转移的结肠癌组织中表达水平最低,在未合并肝转移的结肠癌组织中表达水平居中,三组间差异具有统计学意义.结论 GSR可能影响结肠恶性肿瘤代谢、分期、TP53突变以及结肠癌患者预后.
Abstract
Objective To investigate the impact of GSR on the metabolism of malignant colorectal tumors and its prognostic value for patients with colorectal cancer.Methods Differential proteomics was used to obtain differentially-expressed proteins between colorectal cancer tissues and normal colon epithelial tissues.Key proteins in metabolic path-ways were identified through enrichment analysis and protein-protein interaction(PPI)network analysis,followed by survival analysis and clinical correlation analysis.Tissue microarray chips were created from surgical pathological speci-mens of 120 patients with colorectal cancer and immunohistochemical staining was performed.Results Differential pro-teomics analysis identified a total of 1 209 differentially-expressed proteins.KEGG enrichment analysis revealed that these proteins were significantly enriched in metabolic pathways,with a total of 144 enriched proteins.PPI analysis indi-cated that ADH1A,ADH1B,ADH1C,ADH5,ALDH18A1,ALDH3A1,GSTA1,GSTA2,HPGDS,GSR were key pro-teins in the metabolic pathway of differentially-expressed proteins in colorectal cancer.Survival analysis via GEPIA2 re-vealed that GSR influences the overall survival time of patients with colorectal cancer(P=0.0017,HR=0.45).Analy-sis from the UALCAN database revealed that patients with high GSR expression had lower N-stage,overall stage,and a lower TP53 mutation rate.Immunohistochemical results from the tissue microarray chip showed that GSR expressed highest in normal colon epithelial tissue,lowest in colorectal cancer tissues with combined liver metastasis,and interme-diate in colorectal cancer tissues without combined liver metastasis,with significant differences among the three groups.Conclusion GSR may influence tumor metabolism,staging,TP53 mutation,and the prognosis of patients with malig-nant colorectal tumors.
基金项目
辽宁省教育厅项目(JYTQN2023104)
大连市登峰计划医学重点专科建设项目(大卫发[2021]243号)
NETL
NSTL
万方数据