基于生物信息学分析维甲酸诱导蛋白在胃癌组织的表达及其临床意义  

Expression and clinical significance of retinotic acid induced 14 in gastric cancer based on bioinformatic analyse

作　　者：刘霞[1] 吴楠[1] 邹凤宇 崔秀敏 张瑞[1] 班金豹 Liu Xia;Wu Nan;Zou Fengyu;Cui Xiumin;Zhang Rui;Ban Jinbao(Department of Thoracic Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院胸外科,郑州450052

出　　处：《中华实验外科杂志》2023年第8期1593-1596,共4页Chinese Journal of Experimental Surgery

摘　　要：目的观察维甲酸诱导蛋白(RAI14)在胃癌中的表达并探讨其预后预测价值及临床意义。方法通过癌症基因组图谱(TCGA)数据库下载375例胃癌转录组数据、32例正常胃组织转录组数据及临床相关参数, 利用Wilcoxon秩和检验分析RAI14 mRNA的表达差异, 采用卡方检验分析RAI14表达量与临床病理特征的相关性。通过基因表达交互网站(GEPIA)、生存分析数据库(K-M plotter)及单因素回归分析胃癌患者预后影响因素。其中, 采用Cox回归模型进行单因素和多因素分析。同时, 通过R语言分析基因RAI14的相关通路, 探索其在胃癌中的潜在机制。此外, 通过TIMER数据库分析RAI14 mRNA表达水平与胃癌微环境中免疫细胞的相关性。结果 RAI14 mRNA在胃癌组织中的表达水平显著高于正常组织[4.549(4.037, 5.101)比3.109(2.335, 3.983), Z=16.8, P<0.01], 其表达量与肿瘤分化程度呈正相关(χ2=15.817, P<0.05);TCGA数据库及K-M plotter数据库分析显示胃癌组织中RAI14高表达患者预后差(Log-rank:P<0.05);多因素分析结果显示RAI14表达(风险比=1.718, 95%可信区间:1.159~2.546, P<0.01)是影响胃癌预后的独立因素;京都基因与基因组百科全书(KEGG)通路富集分析结果显示RAI14参与了神经活性配体-受体相互作用通路、磷脂酰肌醇3激酶(PI3K)-蛋白激酶B(Akt)信号通路、钙离子信号通路等相关通路;TIMER数据库分析RAI14 mRNA表达水平与胃癌微环境中的M2型巨噬细胞浸润程度呈正相关(相关系数r=0.441, Spearman’s:P<0.05)。结论 RAI14 mRNA在胃癌组织中高表达, 且与胃癌患者的不良预后密切相关, 可作为胃癌预后的独立危险因子, 其可能通过神经活性配体-受体相互作用通路、PI3K-Akt信号通路、钙离子信号通路等相关通路在胃癌中发挥作用, 同时RAI14可能与胃癌微环境中的M2型巨噬细胞相关。Objective To explore the expression,prognostic value,and clinical significance of retinotic acid induced 14(RAI14)in gastric cancer(GC).Methods The transcriptome data of GC(375 tumor vs 32 normal tissues)and related clinical parameters from the cancer genome atlas(TCGA)database were downloaded.The differences in RAI14 mRNA expression were analyzed using the Wilcoxon rank sum test,and the correlation between RAI14 expression and clinicopathological features was analyzed using the chi-square test.We evaluated the prognostic impact of RAI14 in GC patients using gene expression profiling interactive analysis(GEPIA),the Kaplan-Meier plotter(K-M plotter),and multivariate regression analysis.The cox regression model was used for univariate and multivariate analysis.Furthermore,we investigated the potential mechanisms of RAI14 in GC by analyzing its related pathways and explored its correlation with immune cells in the GC microenvironment by TIMER database.Results The expression level of RAI14 mRNA in GC tissues was significantly higher than that in normal tissues[4.549(4.037,5.101)vs.3.109(2.335,3.983),Z=16.8,P<0.01],and its expression level was positively correlated with tumor grade(χ2=15.817,P<0.05).The analysis of TCGA and K-M plotter databases showed that high RAI14 expression was associated with poor prognosis in GC patients(Log-rank:P<0.05),and multivariate analysis revealed that RAI14 expression[hazard ratio=1.718,95%confidence interval:1.159-2.546,P<0.01]was an independent factor of the prognosis of GC.The kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis showed that RAI14 was involved in several relevant pathways,such as neuroactive ligand-receptor interaction,phosphatidylinositol 3 kinase(PI3K)-protein kinase B(Akt)signaling pathway and calcium signaling pathway.The TIMER database revealed a positive correlation between RAI14 mRNA expression and the infiltration degree of M2 macrophages in the GC microenvironment(r=0.441,Spearman’s:P<0.05).Conclusion RAI14 mRNA is highly expressed in

关 键 词：维甲酸诱导蛋白 胃癌 基因表达 预后价值 巨噬细胞 

分 类 号：R735.2[医药卫生—肿瘤]