基于生物信息学分析HDAC8在结肠癌中的临床意义及其与免疫浸润的关系  

Analysis of clinical significance of HDAC8 in colon cancer and its relationship with immune infiltration based on bioinformatics

作　　者：李怡泉 谢宇斌 胡宏 张燕茹 陈图锋[1] Li Yiquan;Xie Yubin;Hu Hong;Zhang Yanru;Chen Tufeng(Department of Gastrointestinal Surgery,the Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China;Institute of Precision Medicine,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou 510080,China)

机构地区：[1]中山大学附属第三医院胃肠外科,广州510630 [2]中山大学附属第一医院精准医学研究院,广州510080

出　　处：《中华普通外科学文献（电子版）》2024年第4期275-281,共7页Chinese Archives of General Surgery(Electronic Edition)

基　　金：广州市科技计划项目(2023A03J0210)。

摘　　要：目的探讨组蛋白乙酰化修饰基因HDAC8对结肠癌患者预后的影响,及其与免疫浸润的相关性。方法采用单因素和多因素Cox回归、Kaplan-Meier曲线分析HDAC8与结肠癌患者预后的相关性;采用GO富集分析探索HDAC8在结肠癌中的潜在作用;采用ESTIMATE算法、CIBERSORT、ssGSEA分析HDAC8与结肠癌肿瘤免疫浸润的相关性。结果聚类分析将结肠癌患者分为三个亚组,其中Group3的患者预后差。Group3中高表达基因HDAC8与肿瘤免疫微环境和患者预后差相关。HDAC8在结肠癌组织中表达上调(P<0.001),主要与免疫应答、防御反应等生物学过程相关。HDAC8高表达组中ESTIMATE评分、基质评分和免疫评分较低,而肿瘤纯度较高(P<0.01)。HDAC8与树突状细胞、CD8+T细胞、B细胞和NK细胞等多种免疫细胞浸润呈负相关。HDAC8高表达组中树突状细胞活性、成熟评分较低,CD8+T细胞幼稚评分较高,而杀伤功能、耗竭功能评分较低(P<0.001)。结论HDAC8的表达与结肠癌患者预后密切相关,其可能通过介导树突状细胞的成熟障碍影响T细胞成熟,参与形成肿瘤组织中失能的免疫微环境,调控结肠癌的发生与发展。Objective To investigate the prognosis,expression of histone acetylation and its correlation with immune infiltration in colon cancer.Methods Univariate and multivariate Cox regression and Kaplan-Meier curve were utilized to evaluate the relationship between HDAC8 gene expression and prognosis of COAD patients.GO enrichment analysis was performed for the potential role of HDAC8 in colon cancer.The connection between HDAC8 and tumor infiltrating immune cells was analyzed based on ESTIMATE,CIBERSORT and ssGSEA.Results Cluster analysis results showed that three acetylation modification subgroups were identified.The highly expressed HDAC8 in Group3 was upregulated in colon cancer tissues and associated with poor prognosis.HDAC8 was closely associated with tumor immune microenvironment such as stromal,immune scores and tumor purity.HDAC8 expression indicated significantly negative correlations with the infiltration of cells such as dendritic cells,CD8+T cells,B cells and NK cells.It was negatively correlated with the activation,maturation,cytotoxicity and costimulatory scores of dendritic cell and CD8+T cells.Conclusions The expression of HDAC8 is closely related to the prognosis of colon cancer patients.It may affect the maturation of dendritic cells and T cells,participate in the formation of dysfunctional immune microenvironment in tumor tissues,and regulate the development of colon cancer.

关 键 词：结肠肿瘤 组蛋白乙酰化修饰 HDAC8 生物信息学 预后 免疫浸润 

分 类 号：R735.34[医药卫生—肿瘤]