基于TCGA数据库研究CXCR4基因在胃癌中的表达及其对肿瘤微环境的影响  

CXCR4 gene expression and its impact on the tumor microenvironment in gastric cancer based on TCGA database

作　　者：张新哲 余超[2] 朱广玉[2] 熊伟 ZHANG Xinzhe;YU Chao;ZHU Guangyu;XIONG Wei(Graduate School,Bengbu Medical University,Bengbu Anhui 233000;Department of Gastrointestinal Surgery,First People’s Hospital of Hefei,Hefei 230011,China)

机构地区：[1]蚌埠医科大学研究生院,安徽蚌埠233000 [2]合肥市第一人民医院胃肠外科,合肥230011

出　　处：《临床与病理杂志》2024年第11期1475-1487,共13页Journal of Clinical and Pathological Research

基　　金：安徽省中医药传承创新科研项目(2024CCCX084)。

摘　　要：目的:趋化因子家族参与了免疫系统、炎症反应、组织发育等生理和病理过程,趋化因子受体4(C-X-C chemokine receptor type 4,CXCR4)在肿瘤微环境中发挥导向与调控作用。本研究探讨CXCR4基因在胃癌组织肿瘤微环境中的表达情况及其临床意义。方法:下载癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中胃癌转录组数据及临床资料,利用ESTIMATE算法和DESeq2分析CXCR4基因的表达差异,并分析患者临床病理参数。收集2022年8月至2023年8月在合肥市第一人民医院行手术治疗并经病理检查确诊为胃癌的手术组织标本进行反转录聚合酶链式反应(reverse transcription-polymerase chain reaction,RT-PCR)和免疫组织化学染色,验证其表达情况。采用CIBERSORT算法评估CXCR4与免疫细胞浸润的相关性。结果:TCGA数据显示胃癌组织的CXCR4基因表达水平显著高于癌旁组织(P<0.001),CXCR4的表达在肿瘤浸润深度及远处转移方面差异均具有统计学意义(均P<0.05)。CXCR4的表达与肿瘤远处转移及分化程度呈正相关(均P<0.05)。TCGA数据及临床数据Kaplan-Meier生存分析均显示高表达组胃癌患者生存时间明显缩短(分别P=0.003、P<0.001)。免疫细胞浸润分析:记忆B细胞、CD8+T细胞与CXCR4表达均呈正相关(均P<0.05);静息CD4记忆T细胞、活化的树突状细胞、浆细胞、活化的自然杀伤细胞、M0巨噬细胞和活化的肥大细胞与CXCR4表达均呈负相关(均P<0.05)。结论:CXCR4在胃癌中高表达提示预后不良,与肿瘤的进展、转移密切相关,且与免疫细胞浸润相关,可能成为免疫治疗的潜在靶点。Objective:The chemokine family is involved in various physiological and pathological processes including immune regulation,inflammation,and tissue development.C-X-C chemokine receptor type 4(CXCR4)plays a guiding and regulatory role in the tumor microenvironment.This study aims to explore the expression of the CXCR4 gene in the gastric cancer microenvironment and its clinical significance.Methods:Gastric cancer transcriptome data and clinical information were obtained from The Cancer Genome Atlas(TCGA)database.The ESTIMATE algorithm and DESeq2 were used to analyze differential expression of CXCR4 gene and its association with clinicopathological parameters.Surgical gastric cancer specimens collected from Hefei First People’s Hospital between August 2022 and August 2023 were analyzed using reverse transcription-polymerase chain reaction(RT-PCR)and immunohistochemistry to validate gene expression.The CIBERSORT algorithm was applied to evaluate the correlation between CXCR4 expression and immune cell infiltration.Results:TCGA data showed significantly higher CXCR4 gene expression in tumor tissues compared to adjacent non-tumor tissues(P<0.001).CXCR4 expression was significantly associated with tumor invasion depth and distant metastasis(P<0.05),and positively correlated with tumor metastasis and degree of differentiation(P<0.05).Kaplan-Meier survival analysis using both TCGA and clinical data showed that high CXCR4 expression was associated with shorter survival time(P=0.003,P<0.001,respectively).Immune cell infiltration analysis revealed positive correlations between CXCR4 expression and memory B cells as well as CD8+T cells(all P<0.05),while negative correlations were observed with resting memory CD4+T cells,activated dendritic cells,plasma cells,activated nature killer cells,M0 macrophages,and activated mast cells(all P<0.05).Conclusion:High expression of CXCR4 in gastric cancer is associated with poor prognosis and closely linked to tumor progression and metastasis.Its expression is also related to immune cell

关 键 词：胃癌 趋化因子受体4 临床特征 肿瘤微环境 免疫标志物 

分 类 号：R73[医药卫生—肿瘤]