白细胞介素12在肝癌中的差异表达及生物信息学分析

Integrated Bioinformatics Analysis Interleukin-12 Expression and Function in Hepatocellular Carcinoma

目的:通过生物信息学方法分析白细胞介素12(Interleukin-12,IL-12)在肝细胞肝癌组织中的表达及其意义。方法:从肿瘤基因组图谱计划(The Cancer Genome Atlas,TCGA)数据库中获取肝癌样本与对照样本的数据,通过Ualcan在线工具分析IL12A和IL12B基因的表达数据、甲基化情况,筛选共表达基因,并通过GO(Gene Ontology)富集分析、KEGG通路分析确定共表达基因的生物学过程及其相关功能;使用Kaplan-Meier生存分析法分析患者的生存时间及生存率,并绘制表达水平与预后生存曲线。结果:本研究表明与正常的肝脏组织相比较,IL12A在肝癌组织中的表达量显著升高,但IL12B在二者之间没有显著的差异表达。IL12A在肝癌组织中的甲基化程度要明显低于正常组织。同时IL12A在不同肝癌分期中也存在差异表达。与IL12A共表达的基因主要参与了细胞增殖、代谢过程、免疫反应、应激反应等生物学过程,并参与了DNA复制、RNA转运、细胞周期调节、蛋白水解、错配修复等生物学通路。同时IL12A基因表达量高的肝癌患者的生存率明显低于其表达量低的患者。结论:IL12A基因在肝细胞肝癌组织中高表达,并且同肝癌的发生、发展密切相关,其表达量与预后生存率也有相关性;因此,IL12A可以作为肝癌诊断筛选、预后效果预测的标志物之一。

Objective:To analyze the expression and function of interleukin-12(IL-12)in hepatocellular carcinoma(HCC).Methods:The data of IL12A and IL12B expression in normal liver tissue and HCC tissue were obtained from The Cancer Genome Atlas(TCGA)database.The different expression analysis was performed using Ualcan online tool.Gene Ontology function and KEGG pathway analyses were performed for coexpressed genes of IL12A.The prognostic value on IL12A expression of HCC patients was analyzed using Kaplan-Meier method.Results:Compared to normal liver tissue,the mRNA expression level of IL12A was significantly up-regulated in HCC tissue.However,no significantly different expression of IL12B was identified between HCC patients and controls.The higher expression of IL12A was obviously related to lower DNA methylation status.Moreover,the expression levels of IL12A in HCC tissues from patients with different disease stages were significantly different.The enrichment analysis on IL12A and co-expressed genes suggested that those genes in HCC could play roles in cell proliferation,metabolic process,immune system process,response to stimulus and so on,and were involved in DNA replication,RNA transport,mismatch repair and other relative pathways.The overall survival rates in HCC patients with high IL12A expression were significantly lower than those in HCC patients with low IL12A expression.Conclusion:The results showed that IL12A was highly expressed in HCC and were associated with poor survival of HCC patient,and IL12A might play a potential role in the development of HCC,and could be used as a bio-marker for screening and prognosis estimation of HCC.