DHCR7基因在膀胱癌中的表达及其与临床特征及预后关系的生物信息学分析

The expression of DHCR7 gene and its relationships with clinical characteristics and prognosis in bladder cancer based on bioinformatics

目的采用生物信息学技术研究7-脱氢胆固醇还原酶(DHCR7)在膀胱癌中的表达及其与临床预后的关系等。方法采用TCGA、GEO数据库分析膀胱癌与正常膀胱组织中DHCR7基因的表达,利用Human Protein Atlas数据库验证DHCR7蛋白在膀胱癌组织中的表达,通过Kaplan Meier法分析DHCR7基因表达水平与膀胱癌患者预后及生存情况之间的关系;应用GeneMANIA数据库构建蛋白质互作网络(PPI),并通过GEPIA2分析互作基因在膀胱癌中的相关性;依据DHCR7基因mRNA相对表达水平,应用GSEA 4.1.0软件对TCGA数据进行分层基因富集分析。结果膀胱癌组织中DHCR7基因mRNA相对表达水平明显高于癌旁组织及正常膀胱组织,差异有统计学意义(P<0.05);不同肿瘤分期、分级、分子分型膀胱癌组织中DHCR7基因mRNA相对表达水平比较,差异有统计学意义(P<0.05);与DHCR7低表达组相比,DHCR7高表达组的总生存期、肿瘤特异性生存期、无进展生存期更低,差异有统计学意义(P<0.05);PPI及基因富集分析显示DHCR7基因功能主要与胆固醇稳态、MTORC1通路等有关。结论DHCR7基因在膀胱癌中高表达,与临床不良预后密切相关,DHCR7基因可能通过多种机制参与肿瘤发展过程,有望成为膀胱癌干预治疗、预后评估新的靶点。

Objective The expression of 7-dehydrocholesterol reductase(DHCR7)in bladder cancer and its correlation with clinical prognosis were studied by bioinformatics analysis.Methods The expression of DHCR7 gene in bladder cancer and normal bladder tissues was analyzed by TCGA and GEO database,and the expression of DHCR7 protein in bladder cancer tissues was verified by Human Protein Atlas database.Kaplan Meier method was used to analyze the association between DHCR7 gene expression and prognosis or survival status of bladder cancer patients.GeneMANIA database was used to construct protein interaction network(PPI),and the correlation of interacting genes in bladder cancer was analyzed by GEPIA2.According to the stratified expression level of DHCR7 gene,GSEA 4.1.0 software was applied to gene enrichment analysis of TCGA data.Results The relative expression level of DHCR7 gene mRNA in bladder cancer tissues was significantly higher than that in para-cancer tissues and normal bladder tissues(P<0.05).The relative expression level of DHCR7 gene mRNA was significantly different in bladder cancer tissues with different tumor stages,grading and pathological types(P<0.05).Overall survival,disease-specific survival and progression-free survival in the high expression of DHCR7 group were significantly lower than those in the low expression of DHCR7 group(P<0.05).Protein interaction network gene enrichment analysis showed that the function of DHCR7 gene mainly related to cholesterol homeostasis and MTORC1 pathway.Conclusion DHCR7 gene highly expresses in bladder tumors,which relates closely to poor clinical prognosis.DHCR7 gene might be involved in tumor development through multiple mechanisms,it is expected to be a new therapeutic target and prognostic marker of bladder cancer.