摘要
目的利用生物信息学分析方法对基因芯片数据进行分析,筛选出影响黑色素瘤发生发展过程中的核心基因和关键通路,探索其分子机制并发现黑色素瘤潜在生物标志物,为分子诊断、靶向治疗和预后评估提供线索。方法从基因表达数据库(GEO)中筛选数据集,利用GEO2R分析黑色素瘤组织和正常皮肤组织中显著差异表达基因,通过GEPIA平台对TCGA-SKCM和GTEx联合进行差异表达分析。使用Bio vemn获得三组数据共有差异基因,对其进行GO功能注释、KEGG富集、进行蛋白互作分析、筛选关键基因,探讨HDACi治疗黑色素瘤的免疫学机制。结果从GSE3189和GSE15605以及TCGA-SKCM和GTEx联合中有交集的差异表达基因有1015个。主要涉及表皮发育、细胞群体增殖的负调控、上皮细胞分化、循环系统流程、血液循环、皮肤发育、有机羟基化合物代谢过程、超分子纤维组织、负调节细胞粘附、细胞组分形态发生;主要存在于细胞外基质、外部封装结构、Collagen-containing细胞外基质、细胞间连接、角质化包膜、细胞基部、基底质膜、顶端的一部分细胞、顶端质膜、管基底等离子体膜;主要富集在肌动蛋白结合、钙离子结合、分子功能抑制剂活动、细胞外基质的结构组成、酶抑制剂的活动、跨膜受体蛋白酪氨酸激酶活性、肌动蛋白丝绑定、跨膜受体蛋白激酶活性、蛋白质酪氨酸激酶活性、肽酶调节活动。以及显著涉及到的免疫和炎症的通路有癌症中的转录失调、人乳头瘤病毒感染、致病性大肠杆菌感染、PPAR信号通路、花生四烯酸代谢通路,互作较强的核心差异基因有EGFR、ERBB2、CD34、PPARG、SOX9、CDKN2A、EPCAM、AURKA、CCNB1、SPP1。结论癌症中的转录失调、人乳头瘤病毒感染、致病性大肠杆菌感染、PPAR信号通路、花生四烯酸代谢通路可能是HDACi治疗黑色素瘤的免疫学机制关键通路,EGFR、ERBB2、CD34、PPARG、SOX9、CDKN2A、EPCAM、AURKA、CCNB1、SPP1等基因可能在其中发挥着关键作用。
Objective To screen the core genes and key pathways involved in the development and progression of melanoma by bioinformatics analysis of microarray data,to explore the molecular mechanism and find the potential biomarkers of melanoma,which provide clues for molecular diagnosis,targeted therapy and prognostic evaluation.Methods The data sets were selected from gene expression database(Geo),and the differentially expressed genes in melanoma and normal skin tissues were analyzed by GEO2R,the differential expression of TCGA-SKCM and GTEX was analyzed by GEPIA platform.We used Bio VEMN to obtain the common differential genes among three groups of data,and used it for GO functional annotation,KEGG enrichment,protein interaction analysis and screening of key genes to explore the immunological mechanism of HDACI in the treatment of melanoma.Results There were 1015 differentially expressed genes from GSE3189 and GSE15605 and TCGA-SKCM and GTEX combination.It was mainly involved in epidermal development,negative regulation of cell population proliferation,epithelial cell differentiation,circulation system process,blood circulation,skin development,metabolism of organic hydroxyl compounds,supramolecular fibrous tissue,negative regulation of cell adhesion and morphogenesis of cell components It mainly existed in extracellular matrix,outer packaging structure,collagen-containing extracellular matrix,intercellular junction,keratinized envelope,cell base,basal plasma membrane,apical part of cell,apical plasma membrane,tube base plasma membrane;They were mainly concentrated in actin binding,calcium ion binding,molecular function inhibitor activity,structural composition of extracellular matrix,enzyme inhibitor activity,transmembrane receptor protein tyrosine kinase activity,actin filament binding,transmembrane receptor protein kinase activity,protein tyrosine kinase activity,and peptidase regulatory activity.And notably involved in immune and inflammatory pathways were transcriptional dysregulation in cancer,human papillomavirus infection,pathogenic E.coli infection,PPAR signaling,and arachidonic acid metabolic pathways,eGFR,ERBB2,CD34,PPARG,SOX9,CDKN2A,EPCAM,Aurka,CCNB1,SPP1 were the core genes with strong interaction.Conclusion Transcriptional dysregulation,human papillomavirus infection,pathogenic E.coli infection,PPAR signaling pathway and arachidonic acid metabolic pathway may be the key pathways in the immunological mechanism of HDACI in the treatment of melanoma,eGFR,ERBB2,CD34,PPARG,SOX9,CDKN2A,EPCAM,Aurka,CCNB1,SPP1 and other genes may play key roles in this process.
作者
苏俊
战杰
王思夏
景艺迪
龙友琪
武睿睿
孙鹏
SU Jun;ZHAN Jie;WANG Sixia(Department of Medical,The People's Hospital of Runan,Runan,Henan,463300,China)
出处
《实用手外科杂志》
2025年第1期77-81,共5页
Journal of Practical Hand Surgery
基金
2019年辽宁省科技厅自然基金知道计划(项目编号:2019-ZD-0330)。
