细胞凋亡相关基因CD44在甲状腺癌组织中的表达及其与肿瘤侵袭和免疫细胞浸润关系的生物信息学分析  

Bioinformatics analysis on expression of apoptosis related gene CD44 in thyroid carcinoma tissue and its relationship with tumor invasion and immune cell infiltration

作　　者：肖志远 宋冰 马鑫雨 金连辉 郑通 柴芳 XIAO Zhiyuan;SONG Bing;MA Xinyu;JIN Lianhui;ZHENG Tong;CHAI Fang(Department of Thyroid Surgery,First Affiliated Hospital,Jinzhou Medical University,Jinzhou 121001,China;Department of Endocrinology and Metabolic Diseases,First Affiliated Hospital,Jinzhou Medical University,Jinzhou 121001,China;Department of Vocational Health and Environmental Health,School of Public Health,Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]锦州医科大学附属第一医院甲状腺外科,辽宁锦州121001 [2]锦州医科大学附属第一医院内分泌与代谢性疾病科,辽宁锦州121001 [3]锦州医科大学公共卫生学院职业卫生与环境卫生学教研室,辽宁锦州121001

出　　处：《吉林大学学报（医学版）》2023年第2期473-481,共9页Journal of Jilin University：Medicine Edition

基　　金：辽宁省科技厅自然科学基金项目(2021-MS-333)。

摘　　要：目的:通过生物信息学方法探讨细胞凋亡相关基因(ARGs)透明质酸受体蛋白CD44在甲状腺癌(THCA)组织中表达及其与患者临床病理特征和肿瘤浸润淋巴细胞(TILs)的关系,为THCA的诊断和治疗提供新的研究方向。方法:从癌症基因组图谱(TCGA)数据库获得THCA凋亡相关的差异表达基因(DEGs)表达谱,选取表达上调的CD44基因,分析THCA组织和癌旁组织中CD44 mRNA表达水平;采用受试者工作特征(ROC)曲线对THCA组织与癌旁组织进行鉴别;采用基因本体功能注释(GO)、京都基因与基因组百科全书(KEGG)和基因集富集分析(GSEA)对DEGs进行功能及通路富集分析;采用STRING数据库建立蛋白-蛋白互作(PPI)网络,通过Cytoscape软件进行可视化;采用TIMER数据库分析THCA组织中CD44 mRNA表达和TILs浸润丰度之间的相关性;使用R语言分析CD44蛋白表达与免疫检查点的关系。选取110例THCA患者标本,采用免疫组织化学SABC法检测THCA组织及相对应的癌旁组织中CD44蛋白表达情况。结果:TCGA数据库分析,与癌旁组织比较,THCA组织中CD44 mRNA表达水平明显升高(P<0.05);ROC曲线分析,在临界值为6.855时,CD44的灵敏度、特异度和准确性分别为89.71%、75.13%和72.91%;GO和KEGG分析,DEGs主要富集在凋亡相关通路;GSEA分析,DEGs与中性粒细胞脱颗粒反应有关;TIMER数据库分析,THCA组织中CD44 mRNA表达水平与B细胞、巨噬细胞、CD4+T淋巴细胞、树突状细胞和中性粒细胞浸润丰度呈正相关关系(partial. cor>0,P<0.01),与肿瘤纯度和CD8+T淋巴细胞浸润丰度无关(partial. cor≤0,P<0.01);在THCA组织中CD44蛋白表达水平与9个免疫检查点基因呈正相关关系(P<0.01),与1个免疫检查点基因呈负相关关系(P<0.01);免疫组织化学SABC法检测,THCA组织中CD44蛋白阳性表达率高于癌旁组织(P<0.01);THCA组织中CD44蛋白表达与肿瘤直径和淋巴结转移有关(P<0.05),与患者性别、年龄和腺外侵犯无关(P>0.05)。结论:Objective:To discuss the expression of apoptosis-related gene CD44 in the thyroid cancer(THCA)tissue and its relationships with the clinicopathological characteristics of the patients and tumor infiltrating leukocytes(TILs),and to provide new research directions for the diagnosis and treatment of THCA.Methods:The expression spectrum of differentially expressed genes(DEGs)related to THCA apoptosis were obtained from The Cancer Genome Atlas(TCGA)Database.The up-regulated CD44 gene was selected and the expression level of CD44 mRNA in THCA tissue and parancancerous tissue were detected;receiver operating characteristic(ROC)curve was used to identify the THCA tissue and paracancerous tissue;Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)were used to analyze the function and pathway enrichment of DEGs;the protein-protein interaction(PPI)network was established by using STRING Database and visualized by Cytoscape software;the relationship between the expression of CD44 mRNA in THCA tissue and the infiltration abundance of TILs was analyzed by TIMER Database;the relationships between expression of CD44 protein and immune checkpoints were analyzed by R software.A total of 110 samples of THCA patients were selected,the expressions of CD44 protein in THCA tissue and paracancerous tissue were detected by the immunohistochemical SABC method.Results:The TCGA Database analysis results showed that compared with paracancerous tissue,the expression level of CD44 mRNA in THCA tissue was increased(P<0.05);the ROC curve analysis results showed that when the critical value was 6.855,the sensitivity,specificity,and accuracy of CD44 were 89.71%,75.13%,and 72.91%,respectively.The GO and KEGG analysis results showed that the DEGs were mainly enriched in the apoptosis-related pathways;the GSEA analysis results showed that the DEGs were associated with degranulation response of the neutrophils.The TIMER Database analysis results showed that the expression level of CD44 mRNA in THCA tis

关 键 词：甲状腺肿瘤 生物信息学 透明质酸受体蛋白 肿瘤免疫浸润 免疫检查点 

分 类 号：R736.1[医药卫生—肿瘤]