外阴鳞状细胞癌关键基因的筛选及免疫浸润分析  

Screening and immunoinfiltration analysis of key genes in vulvar squamous cell carcinoma

作　　者：申杨 段子博 谭展望[2] 楚健子 祝佩芹 李艳青 李国雷 林晓华 SHEN Yang;DUAN Zibo;TAN Zhanwang;CHU Jianzi;ZHU Peiqin;LI Yanqing;LI Guolei;LIN Xiaohua(Department of Gynecology,The First Affiliated Hospital of Hebei University of Traditional Chinese Medicine,Shijiazhuang 050011,China;Traditional Chinese Medicine Classics Teaching and Research office,College of Integrated Traditional Chinese and Western Medicine,Hebei Medical University,Shijiazhuang 050031,China;Hebei Key Laboratory of Liver and Kidney Disease Research of Integrated Traditional Chinese and Western Medicine,Shijiazhuang 050091,China;Hebei Key Laboratory of Turbidity Toxin Syndrome,Shijiazhuang 050011,China)

机构地区：[1]河北中医药大学第一附属医院妇科,石家庄050011 [2]河北医科大学中西医结合学院中医经典教研室,石家庄050031 [3]河北省中西医结合肝肾病证研究重点实验室,石家庄050091 [4]河北省浊毒证重点实验室,石家庄050011

出　　处：《天津医科大学学报》2024年第5期391-398,共8页Journal of Tianjin Medical University

基　　金：国家自然科学基金青年科学基金项目(81403428);河北省政府资助临床医学优秀人才培养项目(ZF2023156);河北省中医药管理局科研计划项目(2024019)。

摘　　要：目的:利用生物信息学方法筛选外阴鳞状细胞癌(VSCC)的关键基因及分析免疫浸润特征。方法:从GEO数据库中下载VSCC相关基因表达数据,应用差异表达基因(DEGs)分析和加权基因共表达网络分析筛选出共同的DEGs,对DEGs进行富集分析。采用STRING数据库和Cytoscape软件构建蛋白互作(PPI)网络,并通过4种算法筛选出关键基因,进行关键基因GSEA分析。应用CIBERSORT分析VSCC相关免疫细胞浸润特征及关键基因与免疫细胞的相关性。结果:共筛选出182个DEGs,DO富集主要涉及生殖器官良性肿瘤、结缔组织癌等疾病;GO和KEGG富集结果主要与表皮发育、角质化包膜、氧化应激、免疫细胞迁移等有关;PPI网络中有65个节点,90条边,筛选出6个关键基因,S100A7、SPRR2B、SPRR2G、CASP14、CDSN、ESR1,共同富集到了细胞周期、蛋白酶体信号通路。免疫浸润分析结果显示,与对照组相比,VSCC组初始B细胞、静息CD4^(+)T记忆细胞下调(均P<0.05),记忆B细胞、调节性T细胞、活化的NK细胞、巨噬细胞M0型、静息肥大细胞、活化的肥大细胞、嗜酸性粒细胞、中性粒细胞上调(均P<0.05)。Spearman相关性分析显示,S100A7、SPRR2G、CASP14、CDSN均与γδT细胞呈负相关(均P<0.05),与巨噬细胞M0型呈正相关(均P<0.05);ESR1与巨噬细胞M0型呈负相关(P<0.05),与静息CD4^(+)T记忆细胞呈正相关(P<0.05);S100A7、CASP14与静息CD4^(+)T记忆细胞呈负相关(均P<0.05);SPRR2G、CDSN与CD8^(+)T细胞呈负相关(均P<0.05)。结论:S100A7、SPRR2B、SPRR2G、CASP14、CDSN、ESR1可能是VSCC潜在的生物标志物,长期慢性炎症刺激导致表皮终末分化过程异常可能是VSCC发生、发展的关键因素。Objective:The key genes and immunoinfiltration characteristics of vulvar squamous cell carcinoma(VSCC)were screened by bioinformatics methods.Methods:The gene expression data related to VSCC were downloaded from GEO database.Differentially ex-pressed genes(DEGs)analysis and weighted gene co-expression network analysis were used to screen out common DEGs,and en-richment analysis of DEGs was performed.The protein-protein interaction(PPI)network was constructed using STRING database and Cytoscape software,and the key genes were selected by four algorithms,and the key genes were analyzed by GSEA.CIBERSORT was used to analyze the infiltration characteristics of VSCC-related immune cells and the correlation between key genes and immune cells.Results:A total of 182 DEGs were selected,and DO enrichment mainly involved benign tumors of reproductive organs,connective tissue cancer and other diseases.The results of GO and KEGG enrichment were mainly related to epidermal development,keratinized envelope,oxidative stress and immune cell migration.There were 65 nodes and 90 edges in the PPI network,and six key genes were screened out,including S100A7,SPRR2B,SPRR2G,CASP14,CDSN,ESR1.Cell cycle and proteasome signaling pathways were en-riched.Compared with the control group,the initial B cells and resting CD4^(+)T memory cells in the VSCC group were downregulated(all P<0.05),while memory B cells,regulatory T cells,activated NK cells,macrophage M0 type,resting mast cells,activated mast cells,eosinophils,and neutrophils were upregulated(all P<0.05).Spearman correlation analysis revealed that S100A7,SPRR2G,CASP14,and CDSN were all negatively associated with γδT cells(all P<0.05),and positively correlated with macrophage M0 type(all P<0.05).ESR1 was negatively correlated with macrophage M0 type(P<0.05)and positively correlated with resting CD4^(+)T memory cells(P<0.05).S100A7 and CASP14 were negatively correlated with resting CD4^(+)T memory cells(all P<0.05).SPRR2G,CDSN were negatively correlated with CD8^(+)T cells(all P<0.05).Co

关 键 词：外阴鳞状细胞癌 加权基因共表达网络分析 差异表达基因 富集分析 免疫浸润 

分 类 号：R711.72[医药卫生—妇产科学]