摘要
目的:探讨黏蛋白MUC13在胃癌(GC)患者中的预后价值以及对GC细胞生物学行为的影响.方法:TCGA数据库分析MUC基因在GC组织中的表达水平.采用Spearman秩相关分析MUC基因之间表达的相关性,GO功能富集和京都基因与基因组百科全书(KEGG)通路富集探究MUC基因潜在的生物学功能.基于单因素COX回归筛选与GC预后显著相关的MUC基因.通过免疫荧光检测MUC13的表达水平,并分析其与GC预后等临床病理特征的关系.siRNA敲低GC细胞中MUC13后,利用CCK-8、集落形成以及Transwell实验观察其对GC细胞增殖、迁移和侵袭的影响.结果:MUC1、MUC2、MUC3A、MUC4、MCU5B、MUC12、MUC13等基因在GC组织中表达均显著上调(P＜0.05),主要富集在消化系统过程、上皮结构维持、顶端质膜、唾液分泌等途径.其中,MUC13与GC患者的不良预后(Log-rank P＜0.05)、年龄(P＜0.001)及肿瘤大小(P=0.035)密切相关.细胞学实验表明敲低MUC13后,GC细胞的增殖能力明显下降(P＜0.05),但迁移和侵袭能力无显著变化(P＞0.05).结论:高表达的MUC13与胃癌的不良预后密切相关,参与肿瘤进展的调控,是胃癌潜在的治疗靶点和预后标志物.
Abstract
Objective:To explore the prognostic value of MUC13 expression in gastric cancer(GC)patients and its impact on the biological behavior of GC cells.Methods:Comprehensive anal-ysis of the expression pattern of MUC genes in GC tissues based on the TCGA database to screen for differentially expressed genes.Spearman correlation analysis determined the correlation of ex-pression between MUC genes in GC tissues.Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway(KEGG)enrichment analysis were used to explore the potential biological functions of MUC genes.Univariate COX regression analysis was performed to explore the relationship between all differentially expressed MUC genes and the prog-nosis of GC patients to screen out MUC genes that were significantly related to the prognosis of GC.Clinical GC tissue samples were used to further verify the expression of MUC13 through im-munofluorescence,and its relationship with the clinicopathological characteristics and prognosis of GC was analyzed.siRNA was used to silence the expression of MUC13 in GC cells,and the effect of MUC13 on cell proliferation,migration and invasion was analyzed through CCK-8,colony forma-tion and Transwell experiments.Results:Among all MUC members,the expression levels of MUC1,MUC2,MUC3A,MUC4,MCU5B,MUC12,and MUC13 were significantly upregulated in GC tissues(P＜0.05).There are certain interactions between these MUC genes,and they are mainly en-riched in pathways related to digestive system processes,epithelial structure maintenance,apical plasma membrane,saliva secretion,etc.Importantly,upregulation of MUC13 in GC tissues indicates poor patient prognosis(Log-rank P＜0.05).In addition,MUC13 expression was significantly correlat-ed with the age(P＜0.001)of GC patients and tumor size(P=0.035).Further cell function experiments showed that after silencing MUC13,the proliferation ability of GC cells was significantly reduced(P＜0.05),while their migration and invasion abilities were not significantly affected(P＞0.05).Con-clusions:Highly expressed MUC13 is closely related to the poor prognosis of gastric cancer,par-ticipates in the regulation of tumor progression and is a potential therapeutic target and prognostic marker for gastric cancer.
维普
万方数据