Ⅰ型胶原蛋白α1链在弥漫型胃癌免疫细胞浸润中的作用及其对远期生存的影响  

Role of collagen typeⅠalpha 1 chain in immune cell infiltration for diffuse gastric cancer and its impact on long-term survival

作　　者：吴玉霞 侯岩松 焦作义[1] 俞泽元[1] WU Yuxia;HOU Yansong;JIAO Zuoyi;YU Zeyuan(Department of General Surgery,Lanzhou University Second Hospital,Lanzhou 730030,P.R.China)

机构地区：[1]兰州大学第二医院普通外科,兰州730030

出　　处：《中国普外基础与临床杂志》2025年第4期485-492,共8页Chinese Journal of Bases and Clinics In General Surgery

基　　金：甘肃省科技计划项目自然科学基金项目(项目编号:24JRRA326);兰州大学第二医院萃英学子科研培育计划(项目编号:CXYZ2024-19)。

摘　　要：目的探索弥漫型胃癌(diffuse gastric cancer,DGC)的免疫细胞浸润和细胞外基质(extracellular matrix,ECM)的相互作用,寻找新的诊断性生物标志物及治疗靶点。方法分析癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中DGC患者的转录组数据,以筛选与免疫相关和ECM受体相关信号通路的潜在调控因子,分析该调控因子在DGC患者的DGC组织及癌旁胃组织中的差异表达,同时采用生物信息学分析该调控因子与免疫细胞浸润和ECM的关系以及其预后意义;再收集兰州大学第二医院(简称“我院”)的临床病例进行验证。回顾性收集我院2017年1月至2019年12月期间收治的90例DGC患者的DGC组织和癌旁胃组织石蜡标本,采用免疫组织化学染色法检查组织中该调控因子表达,然后分析其表达与免疫细胞浸润、患者临床病理特征和预后的关系;另外收集我院2024年收治的10例DGC患者的DGC组织及其配对的癌旁胃组织,采用实时定量PCR法检测该调控因子mRNA的表达情况。检验水准α=0.05。结果从TCGA数据库中筛选出了与免疫和ECM受体信号通路相关的潜在调控因子——Ⅰ型胶原蛋白α1链(collagen typeⅠalpha 1 chain,COL1A1),它在DGC患者的DGC组织中较癌旁胃组织中高表达(P<0.001),其高表达与较差的预后相关[HR(95%CI)=2.98(1.21,7.30),P=0.017];COL1A1基因表达与CD8+T细胞富集分数成负相关(CIBERSORT算法:r=-0.17,P<0.001;xCELL算法:r=-0.32,P<0.001),与M2型肿瘤相关巨噬细胞富集分数成正相关(CIBERSORT算法:r=0.32,P<0.001;xCELL算法:r=0.24,P<0.001)。临床病例验证:COL1A1蛋白和mRNA在DGC患者的DGC组织中均较癌旁胃组织高表达(P<0.001),且COL1A1蛋白高表达者的总生存情况差于其低表达者(P<0.001),同时其高表达(相对低表达)也是影响DGC患者术后总生存期的危险因素[HR(95%CI)=6.607(3.374,12.940),P<0.001];COL1A1蛋白表达与M2型肿瘤相关巨噬细胞标志物CD163蛋白表达呈正相关(r=0.76,PObjective To explore the interaction between immune cell infiltration and extracellular matrix(ECM)in diffuse gastric cancer(DGC),and to identify novel diagnostic biomarkers and therapeutic targets.Methods Transcriptomic data of DGC patients from The Cancer Genome Atlas(TCGA)database were analyzed to screen potential regulator factor of immune-related and ECM receptor-related signaling pathways.Differential expression of the identified regulator was assessed between the DGC tissues and the adjacent gastric tissues.Bioinformatics analysis was utilized to evaluate the relation between the regulator factor and immune cell infiltration and ECM,as well as prognosis.The clinical validation was performed using 90 paraffin-embedded DGC tissues and adjacent gastric tissu from the patients treated at The Lanzhou University Second Hospital(hereafter“our hospital”)from January 2017 to December 2019.The immunohistochemical staining was employed to examine the expression of regulator factor,followed by analysis of its association with immune cell infiltration,clinicopathologic features,and prognosis.Additionally,10 paired DGC tissues and adjacent gastric tissues from the patients treated in our hospital in 2024 were collected for validation using real-time quantitative PCR to assess mRNA expression.The significance level was set atα=0.05.Results The collagen type I alpha 1 chain(COL1A1),a potential regulator factor linked to immune and ECM receptor signaling pathways,was identified from the TCGA database.The COL1A1 was significantly overexpressed in the DGC tissues compared to the adjacent gastric tissues(P<0.001),and its high expression correlated with poorer prognosis[HR(95%CI)=2.98(1.21,7.30),P=0.017].The COL1A1 gene expression negatively correlated with CD8+T cell enrichment score(CIBERSORT:r=−0.17,P<0.001;xCELL:r=−0.32,P<0.001)but positively correlated with M2 tumor-associated macrophage enrichment score(CIBERSORT:r=0.32,P<0.001;xCELL:r=0.24,P<0.001).The clinical validation confirmed that the COL1A1 protein and m

关 键 词：弥漫型胃癌 Ⅰ型胶原蛋白α1链 免疫细胞浸润 

分 类 号：R735.2[医药卫生—肿瘤]