日光性角化病向鳞状细胞癌演变的关键基因筛选及鉴定  

Screening and Identification of Key Genes in the Evolution of Actinic Keratosis to Squamous Cell Carcinoma

作　　者：张弘扬 董灵娣[2] 杨兵艳 喻楠[2] ZHANG Hongyang;DONG Lingdi;YANG Bingyan;YU Nan(Clinical Medical College of Ningxia Medical University,Yinchuan 750001,China;Department of Dermatology,General Hospital of Ningxia Medical University,Yinchuan 750001,China)

机构地区：[1]宁夏医科大学临床医学院,宁夏银川750001 [2]宁夏医科大学总医院皮肤科,宁夏银川750001

出　　处：《中国皮肤性病学杂志》2025年第2期142-151,共10页The Chinese Journal of Dermatovenereology

基　　金：宁夏回族自治区自然科学基金项目(2022AAC02069)。

摘　　要：目的筛选日光性角化病(actinic keratosis,AK)向鳞状细胞癌(squamous-cell carcinoma,SCC)演变的关键基因,并对其进行生物信息学分析及鉴定。方法从基因表达数据库(gene expression omnibus,GEO)中下载AK与SCC表达谱芯片GSE45216,利用在线工具GEO2R对表达差异基因(differentially expressed genes,DEGs)进行筛选。基于DAVID数据库对DEGs进行GO及KEGG通路富集分析,运用STRING数据库及Cytoscape软件构建蛋白相互作用网络。使用Cytoscape软件筛选枢纽基因,总结其主要功能,并使用GEPIA数据库进行关键基因表达和总生存率的分析。结果在AK与SCC的患者中共筛选出324个DEGs,包括176个上调基因,148个下调基因。差异基因GO分析显示,DEGs主要在调节分子功能(GO:0065009)、调控代谢过程(GO:0009893)和调节细胞通讯(GO:0010646)中富集;KEGG分析显示,DEGs主要富集于细胞基质黏附(hsa04510)、肿瘤蛋白聚糖(hsa05205)和ErbB信号通路(hsa04012)。关键基因包括:MMP1、SMARCE1、RANBP1、GPR68、TGFA、TGFBR3及FMN1。关键基因分析结果显示:3个关键基因(MMP1、RANBP1及GPR68)在SCC中高表达,1个低表达(TGFBR3),MMP1、RANBP1、TGFBR3及FMN1的差异性表达与SCC总体生存率相关。免疫组织化学染色提示,MMP1、RANBP1及GPR68在AK、SCC中表达逐渐升高,而TGFBR3、SMARCE1、TGFA及FMN1的表达未见明显的变化趋势。结论MMP1、RANBP1及GPR68关键基因在AK向SCC演变中具有潜在的基础和临床研究价值。Objective To screen the key genes in the evolution from actinic keratosis(AK)to squamous-cell carcinoma(SCC)for bioinformatics analysis and identification.Methods AK and SCC expression profiling microarrays GSE45216 was downloaded from gene expression omnibus(GEO),and the differentially expressed genes(DEGs)were screened by GEO2R.The DEGs were enriched by GO and KEGG pathway based on DAVID database,and the protein interaction network was constructed by using STRING database and Cytoscape software.Cytoscape was used to screen hub genes,to summarize their main functions,and key gene expression and overall survival were analyzed using GEPIA database.Results A total of 324 DEGs were screened in AK and SCC patients,among which 176 were up-regulated and 148 were down-regulated.Differential gene GO analysis showed that DEGs were mainly enriched in regulating molecular functions(GO:0065009),modulating metabolic processes(GO:0009893),and regulating cellular communication(GO:0010646).KEGG analysis showed that DEGs were mainly enriched in cellular matrix adhesion(hsa04510),tumor proteoglycans(hsa05205)and the ErbB signaling pathway(hsa04012).Key genes included MMP1,SMARCE1,RANBP1,GPR68,TGFA,TGFBR3,and FMN1.The results of key genes analysis showed that three key genes(MMP1,RANBP1,GPR68)were highly expressed in SCC,and one was poorly expressed(TGFBR3).The differential expressions of MMP1,RANBP1,TGFBR3 and FMN1 were correlated with the overall survival rate of SCC.Immunohistochemical staining experiments showed that MMP1,RANBP1 and GPR68 expression gradually increased in AK and SCC,while the expression of TGFBR3,SMARCE1,TGFA and FMN1 did not show a significant trend.Conclusion The key genes of MMP1,RANBP1 and GPR68 have potential basic and clinical value in the evolution from AK to SCC.

关 键 词：日光性角化病 鳞状细胞癌 关键基因 

分 类 号：R739.5[医药卫生—肿瘤]