目的 分析上皮性卵巢癌中拓扑异构酶Ⅱα(TOP2A)的表达与CD4+T细胞数量及临床预后的相关性分析。方法 使用基因信息数据库(GEPIA)、生存分析Kaplan-Meier Plotter和人类蛋白质谱数据库(The Human Protein Atlas)并采用独立样本t检验和卡方检验研究了 TOP2A信使RNA(mRNA)在正常卵巢组织和上皮性卵巢癌(EOC)组织中的表达情况，及与EOC患者Kaplan-Meier生存预后的关联;同时，在基因注释富集数据库中还对TOP2A的共表达基因及其在基因本体(GO)和京都基因与基因组百科全书(KEGG)通路中的富集情况进行了分析。此外，通过免疫相关分析数据库平台及pearson相关性分析研究了 TOP2A基因与CD4+T细胞及其亚群以及其他免疫细胞之间的关系。结果 TOP2A在正常卵巢组织和CD4+T细胞中表达差异无统计学意义(8。60比8。40，t=1。225，P＞0。05)，但在 EOC 组织中显著高表达(4。78±2。63 比 0。44±1。22，|log2FC|＞2，P＜0。05;x2=14。548，P＜0。05);共表达基因的功能富集涉及在有丝分裂细胞周期、PID-E2F途径和转录调控TP53等，而KEGG主要富集在代谢调节过程、正/负反馈调控生物过程、细胞周期以及细胞的生长发育;TOP2A基因的表达与肿瘤细胞纯度以及CD4+T细胞和多种免疫细胞的数量显著相关(r=0。123，P＜0。05);TOP2A组织中高表达不利于EOC患者的生存预后[40个月比48个月，风险比(HR)=1。21，95％可信区间(CI):1。06～1。38，P＜0。05]。但仅有肿瘤微环境浸润CD8+T细胞数量对EOC患者生存预后有显著影响[HR=1。40，95％可信区间(CI):0。98～2。02，P＜0。05]。结论 EOC组织中TOP2A mRNA表达与CD4+T细胞数量呈正相关，且肿瘤浸润CD8+T细胞的低分布不利于EOC患者的生存预后。
Correlation between the expression of the topoisomerase Ⅱ A gene and the abundance of CD4+T cells and clinical prognosis in epithelial ovarian carcinoma
Objective To investigate the correlation between the expression of topoisomerase Ⅱα(TOP2A)gene and the number of CD4+T cells and clinical prognosis in epithelial ovarian cancer(EOC).Methods The expression of TOP2A mRNA in normal ovarian tissue and EOC tissue using by gene expres-sion profile interaction analysis,as well as its prognostic significance for EOC patients by Kaplan-Meier method,were analyzed using the Gene Annotation Resource Database and Kaplan-Meier Plotter databases and independent samples t-or Chi-test of Statistical method.The Human Protein Atlas database was uti-lized to analyze the expression of TOP2A protein in ovarian cancer and normal ovarian tissues.Co-expressed genes of TOP2A,along with their gene ontology(GO)and pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes(KEGG),were examined using GENE and Metascape data-bases.Furthermore,the relationship between the TOP2A gene and CD4+T cells,cell subsets,various im-mune cells were investigated using immune-related databases by pearson correlation analysis.Additionally,the impact of CD4+T cell distribution on survival and prognosis of patients with EOC was assessed by Cox regression analysis.Results There was no significant difference in the expression of TOP2A mRNA and protein between normal ovarian tissue and CD4+T cells(8.60 vs.8.40,t=1.225,P＞0.05),but the expression of TOP2A mRNA and protein was significantly higher in EOC tissue(4.78±2.63 vs.0.44±1.22,|log2FC|＞2,x2=14.548,P＜0.05).The GO function of TOP2A co-expressed genes was mainly concentrated in the mitotic cell cycle,PID-E2F pathway and transcriptional regulation of TP53,while KEGG was mainly concentrated in metabolic regulation,positive/negative feedback regulation of biological processes,cell cycle and cell growth and development.The expression of TOP2A gene was significantly correlated with the purity of tumor cells and the number of CD4+T cells and multiple immune cells(r=0.123,P＜0.05).The high expression of TOP2A in EOC tissues was not conducive to the survival prog-nosis of EOC patients[median survival:40 months vs.48 months,hazard ratio(HR)=1.21,95％confi-denceinterval:1.06-1.38,P＜0.05].However,only the number of CD8+T cells infiltrated by tumor mi-croenvironment had a significant impact on survival and prognosis of EOC patients(HR=1.40,95％confi-dence interval:0.98-2.02,P＜0.05).Conclusion The expression of TOP2A mRNA in EOC tissues is positively correlated with the number of CD4+T cells,and the low distribution of tumor-infiltrating CD8+T cells is not conducive to the survival prognosis of EOC patients.
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