几丁质酶3样1蛋白在胃癌组织的表达及其临床意义

Expression of chitinase 3-like 1 protein in gastric cancer and its clinical significance

目的通过生物信息学探讨几丁质酶3样1蛋白(CHI3L1)在胃癌中的作用及其临床意义。方法利用Oncomine、基因表达谱交互分析(GEPIA)和Kaplan-Meier Plotter等数据库探讨CHI3L1在胃癌中的表达及其与患者生存之间的关系。利用Methsurv数据库分析CHI3L1启动子和CpG位点甲基化水平及其与胃癌临床病理特征的相关性。通过LinkedOmics分析胃癌中CHI3L1共表达网络并进行基因本体和京都基因(GO)和基因组百科全书(KEGG)富集分析。通过分析肿瘤免疫估计资源(TIMER)和肿瘤免疫系统交互数据库(TISIDB)数据库探讨CHI3L1与胃癌免疫浸润之间的关联。体外实验使用细胞计数试剂盒(CCK-8)、Transwell、蛋白质印迹法(Western blot)等方法进一步验证CHI3L1在胃癌中的生物学功能。结果 Oncomine数据库和GEPIA数据库均示CHI3L1在癌组织的表达水平高于正常组织(P<0.05), Kaplan-Meier Plotter数据库也显示CHI3L1表达在胃癌组织中显著增高(P<0.05)并与较低的总体生存率相关(P<0.01)。胃癌组织中CHI3L1的启动子和大部分CpG位点(cg19081101、cg04361579和cg14085262)甲基化水平显着高于正常组织且与患者的生存明显相关。GO和KEGG分析显示CHI3L1共表达相关性较高的前50个基因主要参与免疫反应与代谢调节。在免疫浸润方面, 胃癌患者肿瘤组织中CHI3L1表达与CD8+细胞、B淋巴细胞、树突状细胞和嗜中性粒细胞浸润显著相关。在体外实验中, CHI3L1不仅被证明作为癌基因促进细胞增殖和转移, 且促进PD-L1的表达。结论 CHI3L1的表达上调和甲基化突变位点可能有助于预测胃癌患者的不良预后, CHI3L1能够调控胃癌免疫抑制微环境。

Objective To investigate the role and clinical significance of chitinase 3-like 1 protein(CHI3L1)in gastric cancer through bioinformatics.Methods Using Oncomine,GEPIA,and Kaplan-Meier Plotter databases,the expression of CHI3L1 and its relationship with survival of patients with gastric cancer were studied.Methsurv was used to analyze the methylation level of CHI3L1 promoter and CpG site and their correlation with the clinicopathological characteristics of gastric cancer.The CHI3L1 co-expression network in gastric cancer was analyzed by Linked Omics,and GO and KEGG enrichment analyses were performed.The relationship between CHI3L1 and the immune infiltration of gastric cancer and its underlying mechanism were analyzed by analyzing the tumor immune estimation resource(TIMER)and the tumor immune system interaction database(TISIDB)database.In vitro experiments,cell counting kit-8(CCK-8),Transwell,Western blotting and other methods were used to further verify the biological function of CHI3L1 in gastric cancer.Results Both Oncomine database and GEPIA database showed that the expression level of CHI3L1 in cancer tissues was higher than that in normal tissues(P<0.05).Kaplan-meier Plotter database also showed that CHI3L1 expression was increased in gastric cancer tissues(P<0.05)and associated with lower overall survival(P<0.05).The methylation levels of CHI3L1 promotors and most CpG sites(CG19081101,CG04361579 and CG14085262)in gastric cancer tissues were significantly higher than those in normal tissues and were significantly associated with survival of patients.GO and KEGG analysis showed that the top 50 genes with high co-expression correlation of CHI3L1 were mainly involved in immune response and metabolic regulation.In terms of immune invasion,CHI3L1 expression was significantly correlated with CD8+cells,B lymphocytes,dendritic cells and neutrophil infiltration in tumor tissues of gastric cancer patients.In vitro experiments,CHI3L1 not only promoted cell proliferation and metastasis,but also promoted PD-L1 expression.Conclusion The up-regulation of CHI3L1 expression and methylation mutation sites may help predict the poor prognosis of gastric cancer patients.CHI3L1 can regulate the immunosuppressive microenvironment of gastric cancer.