摘要
目的 本研究旨在通过生物信息学方法探讨G2特异性E3样(G2E3)在肝细胞癌(HCC)中的表达水平及其与预后的关系.方法 应用TCGA分析G2E3在HCC中的表达水平、独立预后价值及其与预后的关系;cBioPortal分析G2E3与甲基化的关系;TIMER分析G2E3与免疫浸润的关系;GEPIA分析G2E3与免疫检查点的关系;GSEA分析G2E3在HCC发生发展中的可能机制.结果 G2E3在HCC组织中的表达显著高于正常肝组织(P<0.05);G2E3高表达组在总生存期、疾病特异性生存期、无进展间隔均显著低于低表达组(P<0.05);G2E3高表达是HCC独立预后危险因素(P=0.018);G2E3的表达与甲基化呈负相关关系(P<0.05);G2E3的表达与6种肿瘤免疫浸润细胞呈正相关关系(P<0.05);G2E3的表达与PD-1、PD-L1、PD-L2、CTLA4的表达呈正相关关系(P<0.05);GSEA分析结果提示G2E3可能通过氧化磷酸化反应、CD22介导的BCR调节、PI3KAKT、Notch、Wnt、Mapk等信号通路调控HCC的发生发展.结论 G2E3在HCC中是高表达的;G2E3的表达与甲基化、免疫浸润及预后不良密切相关;G2E3可能通过多条信号通路调控HCC的发生发展;G2E3可能成为HCC新的诊断和治疗靶点.
Abstract
Objective To explore the expression level of G2-specifc E3-like(G2E3)in hepatocellular carcinoma(HCC)and its correlation with prognosis by bioinformatics analysis.Methods TCGA was used to analyze the expression level and independent prognostic value of G2E3 in HCC,and its relationship with prognosis.MethSurv was performed to assessed the relationship of G2E3 and methylation.TIMER was utilized to detect the correlation between G2E3 expression and immune infiltration.GEPIA was used to investigate the association of G2E3 expression and immune checkpoints.GSEA was used to evaluate the possible mechanism of G2E3 in the development of HCC.Results The expression of G2E3 was higher in HCC tissues than in normal liver tissues(P<0.05).The overall survival(OS),disease specific survival(DSS)and progression-free survival(PFS)of the high G2E3 expression groups were significantly lower than those in low expression groups(P<0.05).G2E3 overexpression was an independent risk factor HCC(P<0.05).G2E3 expression was negatively associated with methylation(P<0.05).G2E3 expression was positively correlated with six kinds of tumorinfiltrating immune cells,and PD-1,PD-L1,and CTLA-4(P<0.05).GSEA enrichment analysis showed that G2E3 might regulate the development of HCC through oxidative phosphorylation,CD22-mediated BCR regulation,PI3KAKT,Notch,Wnt,MAPK and other signaling pathways.Conclusions The expression of G2E3 is up-regulated in HCC and is closely related to methylation,immune infiltration and poor prognosis.G2E3 may regulate the development of HCC though various signaling pathways.G2E3 may be used as a novel diagnostic and therapeutic target of HCC.