拓扑异构酶ⅡαmRNA在乳腺癌中的表达及其临床意义与基因富集分析

摘要

目的 探讨拓扑异构酶Ⅱα(TOP2A)mRNA在乳腺癌中的表达情况及其临床意义,并预测受TOP2A调控而影响乳腺癌发展的基因集.方法 在基因表达汇编数据库中收集GSM42568表达谱数据及对应的临床信息,分析TOP2A mRNA在104例乳腺癌组织和17例正常乳腺组织间的表达情况,以及TOP2A mRNA与乳腺癌临床病理特点的相关性;比较TOP2A mRNA高表达组、低表达组的生存情况;在TOP2A mRNA高表达样本中利用基因富集分析方法预测受TOP2A调控的相关基因集.结果 乳腺癌组织TOP2A mRNA表达水平高于正常乳腺组织(P<0.05);在乳腺癌患者中,TOP2A mRNA的表达与T分期有关(P<0.05),与年龄、肿瘤分级、淋巴结转移状态、雌激素受体状态无相关性(P>0.05).TOP2A mRNA高表达组的中位生存时间及无病生存率低于低表达组(P<0.05).在TOP2A mRNA高表达样本中富集了碱基切除修复、细胞周期、DNA复制、蛋白酶体、RNA降解、剪接体等相关基因集.结论 TOP2A可能是乳腺癌的致癌基因,其能影响乳腺癌患者的预后,有可能成为乳腺癌的新诊疗靶点.%Objective To explore the expression of topoisomerase Ⅱ alpha(TOP2A) mRNA in breast cancer and its clinical significance,and to predict the gene sets regulated by TOP2A influencing the development of breast cancer.Methods GSM42568 expression data and corresponding clinical information were collected from Gene Expression Omnibus database.The expression of TOP2A mRNA was assayed in 104 cases of breast cancer tissues and 17 cases of normal breast tissues.The correlation between TOP2A mRNA and clinicalopathological features of breast cancer was analyzed.The survival was compared between TOP2A mRNA high-expression group and TOP2A mRNA low-expression group.Gene Set Enrichment Analysis was used to predict the relevant gene sets regulated by TOP2A in the samples with TOP2A mRNA high-expression.Results The expression level of TOP2A mRNA in breast cancer tissues was significantly higher than that in the normal breast tissues(P<0.05).In the patients with breast cancer,the expression of TOP2A mRNA correlated with T stage(P<0.05),and did not correlate with age,tumor grade,lymph node metastasis or estrogen receptor status(P>0.05).The median survival time and disease-free survival rate in the TOP2A mRNA high-expression group were lower than those in the TOP2A mRNA low-expression group(P<0.05).Relevant gene sets including base excision repair,cell cycle,DNA replication,proteasome,RNA degradation and splice were enriched in the samples of TOP2A mRNA high-expression.Conclusion TOP2A may be a carcinogen of breast cancer.It can affect the prognosis of patients with breast cancer,and may become a new target for breast cancer.