胃癌中神经纤毛蛋白-1(NRP1)表达及其与肿瘤微环境免疫细胞浸润关系的研究

Study on the expression of neuropilin-1(NRP1)in gastric cancer and its relationship with immune cell infiltration in the tumor microenvironment

目的采用生物信息学分析,探讨神经纤毛蛋白-1(NRP1)在胃癌中的表达与肿瘤免疫微环境中免疫细胞浸润的相关性及其对患者预后的影响。方法应用TIMER数据库分析NRP1在胃癌中的差异性表达,分析NRP1表达与免疫细胞浸润之间的相关性,进一步分析NRP1基因的不同体细胞拷贝数变化与免疫细胞浸润之间的关系,多因素生存分析NRP1表达与肿瘤免疫细胞浸润对胃癌患者预后的影响,最后应用Kaplan-Meier plotter数据库计算不同NRP1表达水平胃癌患者的至第一次进展时间(FP)和总生存期(OS)。结果TIMER数据库基因差异表达分析显示,NRP1在胃癌肿瘤组织中较正常组织中特异性高表达(P<0.001)。其次,Kaplan-Meier plotter生存分析显示高表达NRP1的胃癌患者显示较短的至第一次无进展时间(24.3月对比49.5月,P=0.0059)和总生存期(34.7月对比70.4月,P=0.0036)。进一步分析显示NRP1表达与胃癌肿瘤微环境中的肿瘤纯度呈负相关(r=-0.173,P=7.21e-04),其表达与胃癌微环境中CD8+T细胞、巨噬细胞、树突状细胞、中性粒细胞呈正相关,且差异具有统计学意义。再次,在胃癌中NRP1的体细胞拷贝数变化中的臂及获得与6种免疫细胞的浸润均相关。最后,多因素生存分析显示,在胃癌患者中,NRP1表达(HR:1.43,95%置信区间:1.13-1.82,P=0.003)和巨噬细胞浸润(HR:76.53,95%置信区间:3.43-1705.40,P=0.004)是影响其预后的独立的影响因素。结论NRP1在胃癌中特异性高表达,其高表达是胃癌预后不佳的影响因素,NRP1表达与肿瘤免疫微环境中免疫细胞浸润相关,巨噬细胞浸润和NRP1表达是影响胃癌预后的因素。

Objective Bioinformatics analysis was used to explore the correlation between the expression of neuropilin-1(NRP1)in gastric cancer and the infiltration of immune cells in the tumor immune microenvironment and its impact on patient prognosis.Methods The TIMER database was used to analyze the differential expression of NRP1 in gastric cancer,and analyze the correlation between NRP1 expression and immune cell infiltration,we also analyzed the relationship between somatic copy number alterations(SCNA)of NRP1 gene and immune cell infiltration.Moreover,multivariate survival analysis of the influence of NRP1 expression and tumor immune cell infiltration on the prognosis of patients with gastric cancer.Finally,The Kaplan-Meier plotter database was used to calculate the first progression(FP)and overall survival(OS)of gastric cancer patients with different NRP1 expression levels.Results Gene differential expression analysis showed that NRP1 was specifically expressed in gastric cancer tumor tissues than in normal tissues(P<0.001)in TIMER database.Second,Kaplan-Meier plotter survival analysis showed that gastric cancer patients with high expression of NRP1 showed shorter FP(24.3 months vs.49.5 months,P=0.0059)and OS(34.7 months vs.70.4 months,P=0.0036)than normal patients.Further analysis showed that the expression of NRP1 was negatively correlated with the purity of the tumor in the gastric cancer(r=-0.173,P=7.21 e-04),and its expression was positively correlated with CD8+T cells,macrophages,dendritic cells,and neutrophil cells in the microenvironment of gastric cancer(P<0.05).Third,in gastric cancer,the SCNA of NRP1 all related to the six types of immune cell infiltration in arm-level gain.Finally,multivariate survival analysis showed that in gastric cancer,NRP1 expression(HR:1.43,95%confidence interval:1.13-1.82,P=0.003)and macrophage infiltration(HR:76.53,95%confidence interval:3.43-1705.40,P=0.004)is an independent factor affecting its prognosis.Conclusion NRP1 is specifically and highly expressed in gastric cancer,its high expression is an prognostic factor for patients with gastric cancer.The expression of NRP1 is related to the infiltration of immune cells in the tumor immune microenvironment,and macrophage infiltration and NRP1 expression are factors affecting the prognosis of gastric cancer.