目的通过生物信息学分析方法,探讨GPCR116基因与肺腺癌发生、发展的相关性及其作用机制。方法从GEO数据库下载GSE68465数据集(包含442例肺腺癌组织样本和20例正常组织样本的mRNA数据及基本临床资料)。分析正常组织与肺腺癌组织中GPCR116基因表达量的差异,以及GPCR116基因表达量对肺腺癌患者预后的影响及其与临床特征的相关性;使用基因集富集分析(GSEA)预测GPCR116基因在肺腺癌中参与的信号通路;筛选出差异表达基因(DEGs)进行基因本体论(GO)富集分析及京都基因与基因组百科全书(KEGG)通路富集分析,对GPCR116基因与上调和下调最显著的40个DEGs进行相关性分析;构建PPI网络,分析PPI 网络的中心节点蛋白,筛选出肺腺癌的关键基因。结果(1)与正常组织相比,GPCR116基因在肺腺癌组织中的表达量明显升高;GPCR116表达量是肺腺癌患者预后的独立影响因素,GPCR116高表达组的预后较好,且GPCR116基因的表达量与T分期、N分期及吸烟史相关(均P<0.05)。(2)GPCR116基因高表达组主要富集在溶酶体,低表达组主要富集在细胞周期、P53信号通路、错配修复、卵母细胞减数分裂等信号通路中。(3)共筛选出DEGs 235个,包括下调基因103个,上调基因132个。GO富集分析结果显示:DEGs的生物过程主要涉及细胞核分裂、细胞器裂变、有丝分裂细胞周期相变等;KEGG 通路富集分析结果显示:DEGs主要在人类T细胞白血病病毒1感染、细胞周期、类风湿性关节炎等信号通路中富集。(4)GPCR116的表达量与13个显著性差异基因的表达量呈正相关,与20个显著性差异基因的表达量呈负相关。PPI网络分析共得到10个关键基因(NKX2-1、SFTPB、SFTPC、SCGB1A1、PITX1、FOXM1、MYBL2、CDCA3、TFF1、WIF1)。结论GPCR116基因在肺腺癌组织中显著高表达,且其表达量与肺腺癌患者的预后相关,可作为肺腺癌患者预后的预测因素。P53信号通路、错配修复、溶酶体蛋白等通过调控GPCR116基因的表达而在肺腺癌的发生、发展中发挥重要作用,其作用机制可能与筛选出的10个关键基因有关。
ObjectiveTo investigate the correlation between GPCR116 gene and the occurrence and development of lung adenocarcinoma and its mechanism by bioinformatics analysis. MethodsThe GSE68465 data set (including mRNA data and basic clinical data from 442 lung adenocarcinoma tissue samples and 20 normal tissue samples) was downloaded from the GEO database. To analyze the difference of GPCR116 gene expression between normal tissues and lung adenocarcinoma tissues, as well as the influence of GPCR116 gene expression on the prognosis of lung adenocarcinoma patients and its correlation with clinical features. The gene set enrichment analysis (GSEA) was used to predict the signaling pathways in which the GPCR116 gene participates in lung adenocarcinoma. The differentially expressed genes (DEGs) were screened for gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and the correlation between GPCR116 gene and 40 DEGs with the most significant up-regulation and down-regulation was analyzed. PPI network was constructed to analyze the central node proteins of PPI network and select the key genes of lung adenocarcinoma. Results(1) The expression of GPCR116 gene in lung adenocarcinoma tissues was significantly higher than that in normal tissues. GPCR116 expression was found to be an independent influencing factor for the prognosis of lung adenocarcinoma patients. The high GPCR116 expression group had a better prognosis, and GPCR116 gene expression was correlated with T stage, N stage and smoking history (all P<0.05). (2) The high GPCR116 gene expression group was mainly enriched in lysosomes, while the low expression group was mainly enriched in signaling pathways such as cell cycle, P53 signaling pathway, mismatch repair, and oocyte meiosis. (3) A total of 235 DEGs were screened out, including 103 down-regulated genes and 132 up-regulated genes. The results of GO enrichment analysis showed that the biological processes of DEGs were mainly involved in nuclear division, organelle fission, and mitotic cell cycle phase transformation, etc. And the results of KEGG pathway enrichment analysis showed that DEGs were mainly enriched in signaling pathways such as human T cell leukemia virus 1 infection, cell cycle, and rheumatoid arthritis, etc. (4) The expression of GPCR116 was positively correlated with that of 13 significantly differential genes, and negatively correlated with that of 20 significantly differential genes. A total of 10 key genes were screened out by PPI network analysis (NKX2-1、SFTPB、SFTPC、SCGB1A1、PITX1、FOXM1、MYBL2、CDCA3、TFF1、WIF1). ConclusionGPCR116 gene is significantly highly expressed in lung adenocarcinoma tissues, and its expression is related to the prognosis of patients with lung adenocarcinoma and can be used as a predictor for prognosis of lung adenocarcinoma patients. The P53 signaling pathway, mismatch repair and lysosomal protein play important roles in the occurrence and development of lung adenocarcinoma by regulating the expression of GPCR116 gene, and its mechanisms may be related to the 10 key genes screened out.