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基于生物信息学数据库分析TOP2A在肾透明细胞癌中的表达及临床意义
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Abstract:
目的：探讨拓扑异构酶IIA (Topoisomerase IIA, TOP2A)在肾透明细胞癌(clear cell renal cell carcinoma, ccRCC)组织中的表达及临床意义。方法：通过GEPIA、UALCAN以及Human Protein Atlas (HPA)数据库分析TOP2A在正常肾组织和ccRCC组织中的表达。通过UALCAN数据库进行TOP2A mRNA与ccRCC临床病理特征的相关性分析。采用GEPIA、Kaplan-Meier及UALCAN分析TOP2A表达与ccRCC预后的关系。通过TIMER数据库分析TOP2A表达与ccRCC免疫水平的相关性。以及通过STRING和Metascape数据库分别进行TOP2A蛋白质互作网络的构建及其功能机制的探索。结果：与正常肾组织相比，TOP2A在ccRCC组织中显著高表达(P < 0.05)，且TOP2A mRNA的表达水平与ccRCC的病理分期、临床分期以及淋巴结分期呈正相关。生存分析显示，TOP2A低表达的患者的总体生存率明显高于高表达患者(P < 0.05)。TIMER数据库分析显示TOP2A的表达与B细胞(r = 0.356, P < 0.01)、CD4+ T细胞(r = 0.232, P < 0.01)、CD8+ T细胞(r = 0.285, P < 0.01)、巨噬细胞(r = 0.304, P < 0.01)、中性粒细胞(r = 0.43, P < 0.01)以及树突状细胞(r = 0.466, P < 0.01)的免疫浸润水平呈正相关。此外，通过STRING数据库构建了TOP2A蛋白互作网络，富集功能分析显示TOP2A及其相互作用的基因主要参与细胞代谢过程、正负向调节生物进程、多生物过程、繁殖过程、节律过程、代谢过程、对刺激的反应、生物调节以及生长等途径。结论：TOP2A在ccRCC中高表达，并与其发生发展以及不良预后相关，因此TOP2A可能成为ccRCC的新型治疗靶点及预后标志物。
Objective: To explore the expression and clinical significance of Topoisomerase IIA (TOP2A) in clear renal cell carcinoma (ccRCC). Methods: The mRNA and protein expression of TOP2A in ccRCC tissues were detected using databases including GEPIA, UALCAN and Human protein atlas (HPA). UALCAN database was applied to analyze the correlation between TOP2A mRNA and clinicopathological characteristics of ccRCC patients. The relationship between TOP2A expression and prognosis of ccRCC was analyzed with GEPIA, Kaplan-Meier and UALCAN. TIMER database was used to investigate correlations between TOP2A expression and various types of immune cell infiltration in ccRCC. Additionally, STRING and Metascape databases were used to construct a functional protein interaction network of TOP2A and investigate its functional mechanism. Results: TOP2A expression level in ccRCC tissues was significantly higher than in normal renal tissues (P < 0.05), and TOP2A mRNA expression level was positively correlated with the histological grade, clinical stage and N stage of ccRCC. Survival analysis showed that the overall survival rate of patients with low TOP2A expression was significantly higher than that of patients with high TOP2A expression (P < 0.05). TIMER database shows that the TOP2A expression had a positive correlation with infiltrating levels of B cells (r = 0.356, P < 0.01), CD4+ T cells (r = 0.232, P < 0.01), CD8+ T cells (r = 0.285, P < 0.01), macrophages (r = 0.304, P < 0.01), neutrophils (r = 0.43, P < 0.01) and dendritic cells (r = 0.466, P < 0.01) in ccRCC. In addition, the TOP2A protein interaction network was constructed through the
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