肾透明细胞癌中拓扑异构酶Ⅱα与免疫浸润的关系及相关基因分析

Analysis of immune infiltration and topoisomeraseⅡαand related genes in renal clear cell carcinoma

目的探讨拓扑异构酶Ⅱα(TOP2A)与肾透明细胞癌(KIRC)免疫浸润的关系及相关基因分析。方法采用GEPIA和HPA数据库研究TOP2A基因在KIRC的表达和预后;通过单细胞测序数据和TIMER2.0数据库分析TOP2A基因与免疫浸润的关系;利用STRING、GEPIA2和Sangerbox等数据库分析TOP2A的相关基因;通过Aclibi对TOP2A及其相关基因进行预后风险模型构建与验证。结果TOP2A mRNA和蛋白质在KIRC中表达上调,并与患者的临床分期及不良预后有关,且其在CD8+T细胞、调节T细胞和巨噬细胞等免疫细胞中均表达并与多种免疫细胞的浸润水平呈正相关;此外,TOP2A及其相关基因主要富集在细胞周期、不匹配修复和微管结合等途径;预后风险模型显示,TOP2A高风险组患者的生存率显著降低且与其不良预后密切相关。结论TOP2A与KIRC的发生密切相关,不利于患者生存预后,且与多种免疫细胞浸润有关,可作为KIRC诊断与预后的生物标志物。

Objective To explore the immune infiltration and its association with topoisomeraseⅡα(TOP2A)and related genes in kidney renal clear cell carcinoma(KIRC).Methods First,the expression and prognosis of TOP2A in KIRC were researched using the GEPIA and HPA databases.Second,the relationship between TOP2A and immune infiltration was analyzed using single-cell sequencing data and the TIMER2.0 database.Third,genes related to TOP2A were selected by String,GEPIA2 and Sangbox databases.Finally,the prognostic risk model constructed of TOP2A and its related genes was validated by Aclibi.Results The mRNA and protein expression of TOP2A were up-regulated in KIRC,which was related to the clinical stage and poorer prognosis of patients with KIRC.This gene was expressed in many immune cells,such as CD8+T cells,regulatory T cells,and macrophages,and was positively correlated with the infiltration level of various immune cells.In addition,TOP2A and its related genes were mainly enriched in the cell cycle,mismatch repair,and microtubule-binding pathways.The prognostic risk model showed that patients with KIRC in the high-risk group significantly had significantly reduced rates of poor prognosis.Conclusion The TOP2A gene is closely associated with the occurrence of KIRC,and is related to a variety of immune cell infiltrations.Therefore,it is expected to become a biomarker for the diagnosis and prognosis of patients with KIRC.