胃癌患者标本中副肿瘤抗原Ma2高表达及其预后价值

High expression of paratumor antigen Ma2 in specimens from gastric cancer patients and its prognostic value

目的研究胃癌患者组织样本中副肿瘤抗原Ma2(Paraneoplastic Antigen Ma2,PNMA2)的表达水平及PNMA2的表达水平对胃癌患者的预后价值。方法利用TCGA数据库胃癌患者的RNA-seq数据,分析PNMA2在胃癌患者不同临床病理特征下的表达水平,使用生存分析研究PNMA2对胃癌患者总体生存率及无复发生存率的影响。对PNMA2相关表达的基因进行基因本体论(GO)富集分析,应用基因集富集分析(Gene Set Enrichment Analysis,GSEA)受PNMA2表达影响的信号通路。结果胃癌患者的PNMA2表达水平较癌旁组织高(P<0.001),其表达水平与AJCC分期(P=0.043)、分子亚型(P<0.001)等相关,生存分析提示高表达PNMA2的胃癌患者预后不良,单因素及多因素COX分析提示PNMA2高表达是胃癌患者的独立危险因素(HR=1.75,95%CI:1.05~2.93,P=0.033)。PNMA2高表达激活了上皮间质转换(epithelial mesenchymal transition,EMT)及顶端连接(apical junction,AJ)信号通路。结论PNMA2在胃癌组织中高表达,PNMA2可做为胃癌患者的预后分子标志。PNMA2高表达激活了EMT及AJ信号通路,可能通过这些信号通路促进胃癌的发展,导致了较差的预后。

Objective To investigate the expression level of paraneoplastic antigen Ma2(PNMA2)in tissue samples of gastric cancer and the prognostic value of PNMA2 expression in patients with gastric cancer.Methods By using RNA-seq data of gastric cancer patients from the TCGA database,the PNMA2 expression level in patients with gastric cancer was analyzed according to different clinicopathological characteristics.Survival analysis was used to determine the effect of PNMA2 on the overall survival(OS)and recurrence-free survival(RFS)of gastric cancer patients.Gene ontology(GO)enrichment analysis was perfomred for genes related to PNMA2 expression.Gene set enrichment analysis(GSEA)was used to identify signal pathways affected by PNMA2 expression.Results The PNMA2 expression level in gastric cancer was higher than that in adjacent tissues(P<0.001),and associated with AJCC staging(P=0.043)and molecular subtypes(P<0.001).Survival analysis showed that gastric cancer patients with highly expressed PNMA2 had a poor prognosis.Univariate and multivariate COX analyses suggested that high PNMA2 expression is an independent risk factor for gastric cancer(HR=1.75,95%CI:1.05-2.93,P=0.033).High expression of PNMA2 was shown to activate the epithelial mesenchymal transition(EMT)and apical junction(AJ)signaling pathways.Conclusion PNMA2 is highly expressed in gastric cancer tissues,and therefore can be used as a molecular prognostic marker for gastric cancers.High expression of PNMA2 activates the EMT and AJ signaling pathways,and may thereby promote the progression of gastric cancer,leading to a poor prognosis.