基于癌症基因组图谱数据库挖掘影响前列腺癌预后的关键基因

Key genes affecting prognosis of prostate cancer based on The Cancer Genome Atlas databases

目的:采用生物信息学方法对癌症基因组图谱(TCGA)数据库进行挖掘,寻找影响前列腺癌患者预后的关键基因。方法:TCGA中下载前列腺癌患者相关数据,应用RStudio软件筛选差异表达基因,clusterProfiler包对差异基因进行基因本体论(GO)及京都基因和基因组百科全书(KEGG)富集分析。用基因表达谱交互分析(GEPIA2)从差异基因中筛选出影响前列腺癌患者预后的基因,将筛选出的基因按表达量绘制接受者操作特性(ROC)曲线,将曲线下面积(AUC)>0.7的3个基因按照最佳截断值分为高低表达组,进行生存分析和多因素回归分析,利用timer2.0进行免疫细胞浸润相关性分析。应用χ^(2)检验、Kaplan-Meier分析及Cox回归进行数据分析。结果:筛选出差异表达基因358个。差异基因的GO及KEGG富集分析发现激素代谢过程、肽酶调节活性、雌激素信号通路等功能和通路有差异。通过GEPIA2初步筛选出12个影响前列腺癌总生存期(OS)的差异基因,3个基因符合AUC>0.7,上调基因为孕激素和脂联素分子受体6(PAQR6)及抗苗勒管激素(AMH),下调基因为含铜胺氧化酶1(AOC1)。生存分析结果显示,Gleason评分、PAQR6、AMH及AOC1影响前列腺癌患者的OS(χ^(2)=7.235、13.513、12.264、13.748,P<0.01),多因素Cox回归结果表明,Gleason评分>7分风险比(HR)5.76,95%置信区间(CI)1.04~32.07,P<0.05、PAQR6高表达(HR:11.75,95%CI:1.42~97.11,P<0.05)和AOC1高表达(HR:0.17,95%CI:0.04~0.85,P<0.05)是影响前列腺癌患者OS的独立影响因素。前列腺癌内PAQR6的表达量与CD4+T细胞、CD8+T细胞及B细胞的表达量呈负相关(r=-0.158、-0.200、-0.142,P<0.01)。结论:PAQR6及AOC1在前列腺癌中差异表达,是影响前列腺癌患者预后的独立影响因子。

Objective To explore the key genes affecting the prognosis of patients with prostate cancer based on The Cancer Genome Atlas(TCGA)databases by bioinformatics method.Methods The data of patients with prostate cancer were downloaded from TCGA,and the differentially expressed genes(DEGs)were screened by RStudio software.The DEGs were enriched by Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Gnomes(KEGG)by cluster Profile,and screened by Gene Expression Profiling Interactive Analysis 2(GEPIA2)for prognostic genes for prostate cancer.The receiver operating characteristic(ROC)curve was plotted according to the expression level of the genes.Three genes with area under curve(AUC)>0.7 were divided into high expression group and low expression group according to the optimal cut-off value,and survival analysis and multivariate regression analysis were performed.The correlation of immune cell infiltration was analyzed by timer2.0.Chi-square test,Kaplan-Meier and Cox regression analysis were used for data analysis.Results Totally,358 DEGs were screened.GO and KEGG analysis revealed differences in hormone metabolic proces,peptidase regulator activity,estrogen signaling pathway and other functions and pathways.In total,12 differential genes were screened initially by GEPIA2.Three genes were selected(AUC>0.7),the up-regulated genes were progestin,adipoQ receptor 6(PAQR6)and anti-Müllerian hormone(AMH),and the down-regulated gene was amine oxidase copper-containing 1(AOC1).Survival analysis showed that Gleason score,PAQR6,AMH and AOC1 affected overall survival(OS)in patients with prostate cancer(χ^(2)=7.235,13.513,12.264,13.748,P<0.01).Multivariate Cox regression analysis showed that Gleason score>7[hazard ratio(HR):5.76,95%confidence interval(CI):1.04-32.07,P<0.05],high expression of PAQR6(HR:11.75,95%CI:1.42-97.11,P<0.05)and high expression of AOC1(HR:0.17,95%CI:0.04-0.85,P<0.05)were independent predictive factors for OS in patients with prostate cancer.The expression of PAQR6 in prostate cancer was correlated with the expression of CD4+T cells,CD8+T cells and B cells negatively(r=-0.158,-0.200,-0.142,P<0.01).Conclusion PAQR6 and AOC1 are differentially expressed in prostate cancer,which are independent factors affecting the prognosis of patients with prostate cancer.