USP39在肝细胞癌中的表达及其与预后、免疫浸润的相关性分析

Analysis of the correlation between the expression of USP39 in hepatocellular carcinoma and immune infiltration and prognosis

目的探究去泛素化酶USP39在肝细胞癌(Liver hepatocellular carcinoma,LIHC)中的表达及其与预后、免疫浸润的关系,并预测其生物学功能。方法从癌症基因组图谱(The cancer Genome Atlas,TCGA)数据库和国际癌症基因组协会(The International Cancer Genome Consortium,ICGC)数据库获取原始数据,采用表达差异分析、临床相关性分析、Kaplan-Meier分析、单因素和多因素Cox分析USP39在评估肝细胞癌患者预后中的作用。采用ICGC对USP39在TCGA-LIHC中的表达及生存分析进行验证。应用基因集富集分析(gene-set enrichment analysis,GSEA)软件预测USP39可能参与的分子通路,并分析USP39与潜在靶基因的相关性。通过肿瘤免疫评估资源(Tumor Immune Estimation Resource,TIMER)数据库分析USP39与肝细胞癌免疫浸润的关系。结果USP39在肝细胞癌组织中显著高表达(均FDR<0.05),USP39表达与肿瘤分期,组织学分级和肿瘤大小均具有相关性(均P<0.001);USP39高表达的肝细胞癌患者生存率低于低表达患者,且USP39可作为肝细胞癌患者的独立预后因子(均P<0.05)。GSEA和潜在靶基因相关性分析显示USP39与自噬过程相关,且USP39与ATG4B、ATG16L1、BIRC6、TSC1具有相关性(|r|>0.4,均P<0.001)。TIMER数据库分析显示USP39与免疫细胞浸润具有显著相关性。结论USP39表达与肝细胞癌患者预后及免疫浸润具有相关性,并且其可能通过肿瘤细胞自噬调控肝细胞癌的进展。

Objective To analyze the relationship between expression of deubiquitinating enzymes(USP39)and immune cell infiltration and prognosis in LIHC,and predict its biological function.Methods The original data were collected from TCGA and ICGC.The expression difference analysis,clinical correlation analysis,Kaplan-Meier survival analysis,single-factor and multiple-factor cox analysis were performed to analyze the role of USP39 in assessing the prognosis of LIHC patients.ICGC was used to verify the expression and survival analysis of USP39 in TCGA-LIHC.GSEA software was employed to predict the molecular pathways that USP39 may be involved,and the correlation between USP39 and potential target genes were analyzed.The relationship between USP39 and LIHC immune infiltration was analyzed through the TIMER database.Results The expression of USP39 in LIHC tissues was higher than that in adjacent and normal tissues(all P<0.001),and the expression level of USP39 was relevant to tumor stage,histological grade and T stage(all P<0.001).The survival rate of LIHC patients with high USP39 expression was lower than that of patients with low USP39 expression and USP39 could be used as an independent prognostic factor for evaluating the prognosis of LIHC patients(all P<0.05).GSEA and correlation analysis of potential target genes indicate that USP39 was related to the process of autophagy and had correlation with ATG4B,ATG16L1,BIRC6,TSC1(|r|>0.4,P<0.001).TIMER database analysis results showed that USP39 had a significant positive correlation with immune cell infiltration.Conclusion The expression of USP39 is relevant to the prognosis of LIHC patients and immune cell infiltration.It may regulate the progression of LIHC by autophagy of tumor cell.