胃腺癌进展及预后关键基因与免疫浸润分析

Analysis of Key Genes and Immune Infiltration Affecting the Progression and Prognosis of STAD

目的基于肿瘤研究公共数据库TCGA和GTEx的样本RNASeq数据信息鉴定在胃腺癌中异常表达且与预后相关的关键基因,并探讨其与免疫细胞浸润的相关性,旨在寻找新的诊治靶点。方法应用GEPIA 2.0可视化肿瘤数据分析平台,对公共数据库中胃腺癌及癌旁组织的差异表达基因和预后相关基因进行分析,并筛选出胃腺癌中差异表达并与预后相关的基因,使用FunRich软件进行GO和KEGG富集分析,通过TIMER 2.0和TISIDB分析关键基因表达与免疫细胞浸润的相关性。结果共筛选到4644个差异表达基因,包括3746个上调基因和898个下调基因。与胃腺癌总生存期(OS)和无病生存期(DFS)相关的前500个基因中GFRA3、APBB1、ABCA8、PLCXD3、FAM153B、CLRN3、CD300LG及ASF1B 8个基因差异表达。经过进一步验证确定ABCA8、PLCXD3、CLRN3、CD300LG及ASF1B 5个关键基因,ABCA8、PLCXD3和CD300LG在胃腺癌组织低表达,CLRN3和ASF1B在胃腺癌组织高表达(P<0.01);在胃腺癌中ABCA8、PLCXD3和CD300LG低表达患者OS和DFS较长,CLRN3和ASF1B高表达患者OS和DFS较长(P<0.05)。相关性分析发现以上5个关键基因表达与免疫细胞浸润水平、丰度具有相关性(P<0.01),且预后风险模型单因素Cox回归分析显示以上5个关键基因是胃腺癌预后的相关风险因素(P<0.05,P<0.01)。结论ABCA8、PLCXD3、CLRN3、CD300LG和ASF1B 5个基因在胃腺癌中异常表达,且与预后相关;其表达与免疫细胞浸润具有相关性,可作为预后风险模型的相关风险因素。

Objective To identify key genes that are abnormally expressed in stomach adenocarcinoma(STAD)and related to prognosis based on the data information of RNASeq samples from the public oncology research database TCGA and GTEx,and to explore its correlation with immune cell infiltration,in order to find new diagnostic and therapeutic targets.Methods The GEPIA2 visual analysis platform of tumor data was used to analyze the differentially expressed genes and prognosis-related genes in STAD and adjacent tissues in the public database,and to screen out the differentially expressed genes and prognosis related genes in STAD.GO and KEGG enrichment analyses were performed by FunRich software,and then the correlation between key gene expression and immune cell infiltration was analyzed by TIMER2.0 and TISIDB.Results A total of 4644 differentially expressed genes were screened,including 3746 up-regulated genes and 898 down-regulated genes.Among the first 500 genes related to overall survival(OS)and disease-free survival(DFS),GFRA3,APBB1,ABCA8,PLCXD3,FAM153B,CLRN3,CD300LG and ASF1B were differentially expressed.Through further verification,five key genes,ABCA8,PLCXD3,CLRN3,CD300LG and ASF1B,were identified.ABCA8,PLCXD3 and CD300LG were low expressed in STAD,and CLRN3 and ASF1B were high expressed in STAD(P<0.01).In STAD,the OS and DFS were longer in patients with low expression of ABCA8,PLCXD3 and CD300LG,and longer in patients with high expression of CLRN3 and ASF1B(P<0.05).Correlation analysis found that the expression of the above five key genes was correlated with the level and abundance of immune cell infiltration(P<0.01),and the univariate Cox regression analysis of the prognostic risk model showed that the above five key genes were risk factors for the prognosis of STAD(P<0.05,P<0.01).Conclusion ABCA8,PLCXD3,CLRN3,CD300LG and ASF1B genes are abnormally expressed in STAD and are associated with prognosis.Its expression level is correlated with immune cell infiltration,which can be used as a related risk factor in prognostic risk model.