丝氨酸蛋白酶抑制剂(SERPIN)家族在脑胶质瘤中的免疫相关性及预后价值的生物信息学分析

Bioinformatic analysis of immune correlation and prognostic value of SERPINs in glioma

目的 分析丝氨酸蛋白酶抑制剂(SERPIN)基因家族在胶质瘤中的表达、免疫浸润情况及其与预后的相关性。方法通过利用R语言及多个生物信息学分析数据库,探究SERPIN家族35个基因在癌症基因组图谱(TCGA)胶质瘤肿瘤组织中的变化;选择差异显著的基因,在基因表达谱动态分析(GEPIA)数据库中分析各候选基因高、低表达肿瘤患者的总生存期(OS)和无病生存期(DFS)差异,并进一步筛选最具有预后评价价值的基因;通过肿瘤免疫评估资源2.0(TIMER2.0)数据库及肿瘤微环境单细胞转录组学(TISCH)数据库分析基因在泛癌水平表达、在肿瘤组织内细胞集群富集情况及巨噬细胞与胶质瘤内部SERPIN基因表达浸润的相关性,探究SERPIN与肿瘤免疫之间的关系。结果 SERPIN家族中多个基因的表达量均在胶质瘤中有不同程度的改变,且与胶质瘤分级,预后显著相关。其中丝氨酸蛋白酶抑制剂E2(SERPINE2)、丝氨酸蛋白酶抑制剂H1(SERPINH1)与高级别胶质瘤患者预后存在明显相关性,且二者可能通过对免疫细胞的不同交互途径参与肿瘤免疫微环境内部的免疫调控。结论 SERPIN基因家族的表达同胶质瘤患者的临床预后,肿瘤免疫活动存在密切联系,其中SERPINE2、 SERPINH1为效应显著的关键基因。

Objective To investigate the expression of serine protease inhibitors(SERPINs)and immune infiltration in gliomas and ide ntify their relati on ship with the prog no sis.Methods By using R and several bioinformatics analysis databases,the expression of 35 genes of Serpins in glioma tissues from TCGA were collected and analyzed;In GEPIA,genes with significant d iff ere nces were selected for survival an alysis and genes with the most prognostic value were chose n for further analysis.To probe the correlation between SERPIN and tumor immunity,gene expression in pan-cancer,cells cluster enrichment in tumor tissue,and the correlation between macrophage infiltration and SERPIN expression were analyzed,via TIMER and TISCH.Results The expression of SERPIN in glioma changed,showing a significant correlation with glioma grade and prog no sis.SERPINE2 and SERPINH1 were sign ifica ntly correlated with the prog nosis of patients with high-grade glioma,and may involve in the immune regulati on within the tumor immune microe nvironmen t through d iff ere nt pathways with immune cells.Conclusion The expression of SERPINs are closely related to the clinical prognosis and immunity in glioma,among which SERPINE2 and SERPINH1 are the key genes with significant effect.