基于TCGA数据库分析整合素αV在胃癌中的表达差异及临床意义

Analysis of the Expression and Clinical Significance of IntegrinαV in Gastric Cancer Based on TCGA Database

目的利用癌症基因组图谱(the cancer genome atlas,TCGA)数据库分析整合素αV(integrinαV,ITGAV)在胃癌中的表达差异及临床意义。方法在TCGA数据库获取胃癌临床病例资料及对应的ITGAV mRNA转录组数据,利用R软件分析ITGAV在胃癌组织样本及正常胃组织样本中的mRNA表达差异,分析其表达差异与胃癌患者临床病理特征及预后的关系。基因集富集分析(gene set enrichment analysis,GSEA)预测ITGAV在胃癌中调控的可能信号通路。结果ITGAV在胃癌组织中的mRNA表达量显著高于正常胃组织(W=3161,P=8.837×10^(-6))。ITGAV的表达水平与胃癌患者的T分期、N分期、病理分期及分化程度相关(P<0.05)。ITGAV高表达组的患者的生存时间显著短于ITGAV低表达组患者(P=0.00049)。单因素分析结果显示T分期、N分期、M分期、病理分期、年龄及ITGAV表达量与胃癌的预后相关(P均<0.05)。多因素分析结果显示ITGAV的表达水平与年龄是影响胃癌患者预后的独立危险因素(P均<0.05)。ITGAV mRNA高表达样本富集到Janus激酶/信号转导与转录激活子(Janus kinase/signal transducer and activator of tranions,JAK STAT)信号通路、Toll样受体4(Toll-like receptor 4,TLR4)信号通路、转化生长因子(transforming growth factoryβ,TGF-β)信号通路、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、趋化因子(Chemokine)信号通路、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路、erb-b受体酪氨酸激酶(erb-b tyrosine kinase receptor,ERBB)信号通路及血管内皮生长因子(vascular endothelial growth factor,VEGF)信号通路上调(P均<0.05)。结论ITGAV在胃癌组织中高表达,且ITGAV表达水平与胃癌恶性程度及不良预后具有一定的相关性,并通过上调JAK STAT等信号通路在胃癌中发挥作用。

Objective To investigate the differential expression and clinical significance of integrinαV(ITGAV)in gastric cancer based on the cancer genome atlas(TCGA)database.Methods Gastric cancer dataset and ITGAV mRNA transcriptome data were collected from TCGA database.The differential expression of ITGAV mRNA in gastric cancer tissues and normal gastric tissues were analyed by software R.Moreover,relationship between ITGAV mRNA differential expression and clinicopathological features,prognosis were analyzed by statistic software R.Gene set enrichment analysis(GSEA)was used to predict the possible signal pathways of ITGAV in gastric cancer.Results ITGAV mRNA expression in gastric cancer tissue was significantly higher than that of normal gastric tissue(W=3161,P=8.837×10^(-6)).The expression of ITGAV was associated with T stage,N stage,pathological stage and differentiation degree with gastric cancer patients(P<0.05).The survival time of patients in the ITGAV high expression group was shorter than that of ITGAV low expression group(P=0.00049).Univariate analysis results showed that T stage,N stage,M stage,pathological stage,age and ITGAV expression level were related with prognosis of gastric cancer(all P<0.05).Multivariate analysis results showed that ITGAV expression level and age were independent risk factors for prognosis(all P<0.05).GSEA research results showed that the ITGAV mRNA high expression samples were enriched into the up regulation of Janus kinase/signal transducer and activator of tranions(JAK STAT)signaling pathway,Toll-like receptor 4(TLR4)signaling pathway,transforming growth factoryβ(TGF-β)signaling pathway,mitogen-activated protein kinase(MAPK)signaling pathway,Chemokine signaling pathway,mammalian target of rapamycin(mTOR)signaling pathway,erb-b tyrosine kinase receptor(ERBB)signaling pathway and vascular endothelial growth factor(VEGF)signaling pathway(all P<0.05).Conclusion ITGAV is high expression in gastric cancer tissues.ITGAV expression level is associated with the malignant degree and poor prognosis of gastric cancer.Moreover,it plays an important role in gastric cancer by activating JAK STAT signaling pathways.