对参与肺腺癌发生的核心基因的综合生信分析

Integrative Bioinformatics Analysis Identified Hub Genes in Association with Development of Lung Adenocarcinoma

目的:侵袭性的肺腺癌(LUAD)是引起肺癌死亡的主要原因之一。因此,鉴定重要的LUAD相关基因及进一步分析其预后意义对于LUAD患者的生存率至关重要。方法:采用加权基因共表达网络分析(WGCNA)和差异基因表达分析方法,从TCGA-LUAD数据库和GEO的GSE32863筛选出有差异的共表达基因,对其进行功能富集分析和蛋白质相互作用网络(PPI)分析。此外,通过应用Cytoscape的CytoHubba插件来识别12个核心基因进行生存分析和肿瘤分期相关性的分析。结果:从TCGA和GEO数据库中共提取了358个差异共表达基因。这些基因在GO分析中主要富集于细胞外结构组织,细胞–细胞连接和DNA结合转录酶激活活性。在KEGG分析中,主要富集于药物代谢–细胞色素P450。此外,在PPI网络中鉴定了12个核心基因。在LUAD患者中,ADCY4、VIPR1和TGFBR2的表达水平与临床分期和整体生存率(OS)相对应。结论:ADCY4、VIPR1和TGFBR2可能在肿瘤发生中起重要作用,因此它们可作为LUAD的预后生物标志物和治疗靶点。

Objective: Lung cancer-related death is mainly caused by lung adenocarcinoma (LUAD), an aggressive malignant tumor. Therefore, the identification of important LUAD-related genes and the further analysis of its prognostic significance are critical for the survival of LUAD patients. Method: Weighted Gene Co-expression Network Analysis (WGCNA) and differential gene expression analysis methods were adopted to screen out TCGA-LUAD database and the gene expression profiles of GSE32863 from GEO. Functional annotation analysis and protein-protein interaction (PPI) network were conducted on differential co-expression genes. Furthermore, survival analysis was carried out on twelve hub genes that were identified by applying the CytoHubba plugin of Cytoscape. Results: A total of 358 differential co-expression genes were extracted from the database of TCGA and GEO. These genes were mainly enriched in extracellular structure organization, cell-cell junction and DNA-binding transcription activator activity. In the KEGG analysis, the main pathways were Drug metabolism-cytochrome P450. Moreover, in a PPI network, the 12 hub genes were identified. The expression level of ADCY4, VIPR1, and TGFBR2 was corresponded with clinical stages and overall survival (OS) in LUAD patients. Conclusion: ADCY4, VIPR1 and TGFBR2 may play an important role in the mechanism of the tumorigenesis, so they will serve as prognostic biomarkers and therapeutic targets of LUAD in the future.