利用生物信息学分析剪切因子QKI在胃腺癌中的表达及意义

Expression and SigniHcance of Splicing Factor QKI in Stomach Adenocarcinoma by Bioinfbrmatics Analysis

目的利用生物信息学技术探讨胃腺癌(Stomach adenocarcinoma,STAD)预后相关的可变剪切(Alternative spli-cing,AS)事件,筛选预后相关的特异性剪切因子(Splicing factor,SF)QKI,为深入研究QKI在胃腺癌中的作用提供理论依据。方法TCGA数据库下载STAD相关数据,R语言构建可变剪切事件与剪切因子调控网络(AS-SF调控网络),生存分析筛选STAD预后相关剪切因子,TCGA与GEO数据比较胃腺癌中癌组织与癌旁组织的表达差异;GEPIA网站获取相关基因,R语言进行功能注释;TIMER在线工具分析在胃腺癌中特异性剪切因子与免疫微环境的相关性。结果通过构建AS-SF调控网络,筛选出胃腺癌中特异性剪切因子QKI,CELF2,SNRPN,BAG2O生存分析提示剪切因子QKI对胃腺癌患者的预后具有显著影响(P<0.05),QKI高表达组的胃腺癌患者总生存率更低。差异分析结果显示QKI在胃腺癌肿瘤组织的表达水平明显高于正常组织,QKI的表达与临床T分期有关。基因富集分析表明QKI主要富集在细胞周期等相关代谢通路。TIMER在线工具分析提示QKI的表达和拷贝数变异(Copy number variation,CNV)可以影响多种免疫细胞特别是巨噬细胞、树突细胞的免疫浸润。结论胃腺癌中存在可变剪切网络,特异性剪切因子QKI在胃腺癌中高表达并与胃腺癌患者的不良预后相关。在胃腺癌免疫微环境(Tumor immune microenvironment,TIME)中QKI的表达和拷贝数变异能够影响免疫细胞的浸润。

Objective To explore alternative splicing(AS)events associated with prognosis in stomach adenocarcinoma(STAD)and to screen for prognosis-related critical splicing factors(SF)QKI.Providing a theoretical basis for studying the role of QKI in STAD.Methods The survival analyses was used to screen for STAD prognosis-related SF.TCGA and GEO data were used to compare the expression differences between tumor and paraneoplastic tissues in stomach adenocarcinoma.The GEPIA website was used to obtain relevant genes,and R language for functional annotation.TIMER online tool was used to analyze the correlation of specific splicing factor with the immune microenvironment of stomach adenocarcinoma.Results We Screened for specific SFs QKI,CELF2,SNRPN and BAG2 in STAD by constructing an AS-SF regulatory network.Survival analysis suggested that QKI had a significant effect on the prognosis of STAD patients(P<0.05),and the overall survival(OS)of STAD patients in the QKI low expression group was better than the high expression group.The results of the Variance analysis showed that the expression level of QKI was significantly higher in tumor tissues than that in nonnal tissues.QKI expression was associated with T-stage.Enrichment analysis showed that QKI was mainly enriched in cell cycle related metabolic pathways.Analysis of the TIMER online tool suggested that QKI expression and copy number variation(CNV)could affect the immune infiltration of a variety of immune cells,particularly macrophage and dendritic cell.Conclusion The presence of an AS-SF network in STAD.High expression of splicing factor QKI in STAD is associated with poor prognosis.QKI expression and CNV can influence immune cell infiltration in STAD.