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胃癌组织 ATP1 A2的表达及机制探讨

         

摘要

Objective To observe the expression of ATP1A2 in gastric cancer tissues and to investigate the correla-tions of ATP1A2 expression with focal adhesion , cell adhesion molecules , calcium signaling and ECM receptor interaction pathways.Methods TCGA dataset which included 293 cases, and GEO dataset GSE62254 which included 300 cases, were collected.ATP1A2 expression was trisected into 3 levels: low, median, and high.The cutoff was set to 0.33 and 0.67.The relationships between ATP1A2 and clinicopathological characteristics as well as prognosis were assessed .GSEA was used to predict the functional gene sets modulated by ATP 1A2.Results There were 95 cases of low expression , 99 of median expression and 99 of high expression in TCGA dataset .The expression of ATP1A2 was significantly associated with T stage, lymph node metastasis, TNM stage and differentiation (all P<0.01), but was not associated with gender and age (all P>0.05).The median survival durations were 70, 36.9, and 26 months in low, median, and high ATP1A2 expres-sion subgroups, respectively.The P value was less than 0.05 in the log-ranked test.While in GSE 62254 dataset, there were 99 low expressed, 102 median expressed and 99 high expressed cases.Different expression of ATP1A2 was signifi-cantly associated with gender , age, T stage, N stage, pTNM stage and Lauren types (all P<0.05).The median survival duration in the high ATP1A2 subgroup was 31 months, while it was much longer in the median and low expression sub-groups (P<0.01).In GSEA, focal adhesion, cell adhesion molecules, calcium signaling, and extracellular matrix recep-tor interaction pathways were enriched in samples with high ATP 1A2 expression (P<0.05 or P<0.01).Conclusions ATP1A2 is highly expressed in gastric cancer tissues and the high expression indicates poor prognosis .The underlying mechanism might be that the high expression of ATP 1A2 causes the abnormity of focal adhesion , cell adhesion molecules , calcium signaling and extracellular matrix receptor interaction pathways .%目的:观察胃癌组织ATP酶α2亚基( ATP1A2)表达情况,探讨其与黏着斑通路、细胞黏附分子、钙离子通路、细胞外基质相关信号通路的关系。方法从癌症基因组图谱( TCGA)数据库下载并预处理胃癌RNASeqV2数据、从人类肿瘤相关基因表达汇编( GEO)数据库下载胃癌样本数据集GSE62254的series matrix数据,通过TCGA数据集纳入胃癌患者293例,通过GEO数据集纳入胃癌患者300例。根据表达谱数据,将胃癌组织ATP1A2表达由低到高排序,按33%、67%者将数据三等分,低于33%者为低表达,高于67%者为高表达,两者之间为中表达。分析不同ATP1A2表达与胃癌患者临床病理参数的关系,比较低、中、高表达者中位生存时间,利用基因集富集分析方法预测ATP1A2相关的基因通路。结果 TCGA数据集纳入的293例胃癌患者中,ATP1A2低、中、高表达者分别为95、99、99例;不同ATP1A2表达与胃癌患者性别、年龄无关(P均>0.05),与T分期、N分期、pTNM分期及组织分化程度有关(P均<0.05);ATP1A2低、中、高表达者中位生存时间分别为70、36.9和26个月,三者间比较P<0.01。 GEO数据集纳入的300例胃癌患者中,ATP1A2低、中、高表达者分别为99、102、99例;不同ATP1A2表达与胃癌患者性别、年龄、T分期、N分期、pTNM分期及Lauren分型均有关(P均<0.05);ATP1A2高表达者的中位生存时间为31个月,较低表达和中表达者中位生存时间明显延长(P<0.01)。 ATP1A2高表达富集了黏着斑通路、细胞黏附分子、钙离子信号通路、细胞外基质等相关的基因通路(P<0.05或<0.01)。结论胃癌组织中ATP1A2高表达,其高表达预示患者预后不良;ATP1A2高表达导致黏着斑通路、细胞黏附分子、钙离子信号通路、细胞外基质等基因通路异常可能是其作用机制。

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