摘要
目的通过生物信息学方法鉴定口腔鳞状细胞癌(OSCC)差异甲基化区域(DMR)中的基因和其生物学特性,并进一步探讨DMRs中的关键基因在预后中的潜在临床应用价值。方法DNA甲基化分析数据集GSE87053下载自GEO数据库。应用R软件对GSE87053行数据归一化和质控后筛选出差异甲基化位点(DMP),并将其聚类以得出DMRs。应用wANNOVAR工具对DMRs行基因注释。通过DAVID数据库行基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集分析,以明确基因的生物学特性。通过STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,同时应用Cytoscape软件的MCODE模块鉴定出PPI中的关键基因。最后,通过GEPIA数据库对关键基因行Kaplan-Meier分析,明确关键基因与OSCC患者总生存期(OS)的相关性。结果DNA甲基化分析数据集GSE87053中包含10例正常样本和11例OSCC样本,共筛选出93650个DMPs(qvalue<0.05),并聚类得出168个DMRs(fwer<0.05)。DMRs中注释得出的194个异常甲基化基因于GO分析中在转录和转录因子活性等条目显着富集(pvalue<0.05),于KEGG通路分析中在癌症通路和Notch信号通路等条目显着富集(pvalue<0.05);PPI网络与Cytoscape软件的MCODE模块分析鉴定出CTBP1、RUNX1、NCOR2、CTBP2和HDAC4可作为基于DMRs分析中的OSCC关键基因。进一步Kaplan-Meier分析显示,CTBP1和HDAC4与OSCC患者的OS相关(P<0.05)。结论基于DMRs分析的OSCC关键基因CTBP1和HDAC4可作为潜在的预后生物标志物或临床靶标,但仍需进一步研究来验证和阐明这些基因在OSCC中的生物学功能。
Objective To identify the genes in the differentially methylated regions(DMR)of oral squamous cell carcinoma(OSCC)and their biological characteristics through bioinformatics methods,and to explore the potential clinical application value of key genes in DMRs in the prognosis.Methods The DNA methylation analysis data set GSE87053 was downloaded from the GEO database.R software was used to normalize and quality control the GSE87053 data set,and screen out differentially methylated positions(DMP)to cluster them to obtain DMRs.Use the wANNOVAR tool to annotate DMRs.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed through DAVID database to clarify the biological characteristics of genes.Construct a protein-protein interaction(PPI)network through the STRING database,and use the MCODE module of Cytoscape software to identify key genes in PPI.Finally,Kaplan-Meier analysis of key genes was performed through the GEPIA database to clarify the correlation between key genes and overall survival(OS)of OSCC patients.Results The DNA methylation analysis data set GSE87053 included 10 normal samples and 11 OSCC samples.A total of 93650 DMPs(Qvalue<0.05)were screened out,and 168 DMRs were obtained by clustering(fwer<0.05).The 194 abnormally methylated genes annotated in DMRs were significantly enriched in entries such as transcription and transcription factor activity in GO analysis(Pvalue<0.05),and were significantly enriched in entries such as cancer pathway and Notch signaling pathway in KEGG pathway analysis(Pvalue<0.05).PPI network and Cytoscape MCODE module analysis identified CTBP1,RUNX1,NCOR2,CTBP2 and HDAC4 as key genes for OSCC in DMRs based analysis.Further Kaplan-Meier analysis showed that CTBP1 and HDAC4 were related to OS in patients with OSCC(P<0.05).Conclusion The key OSCC genes CTBP1 and HDAC4 based on DMRs analysis can be used as potential prognostic biomarkers or clinical targets,but further studies are needed to verify and clarify the biological functio
作者
王婷婷
温凌杜
王子弘
李孔亮
古妍琪
杨宏宇
WANG Ting-ting;WEN Ling-du;WANG Zi-hong;LI Kong-liang;GU Yan-qi;YANG Hong-yu(Stomatological Center,Peking University Shenzhen Hospital,Shenzhen 518000,Guangdong,China;Department of Stomatology,Shenzhen Baoan Maternal and Child Health Hospital,Shenzhen 518000,Guangdong,China;School of Public Health,Southern Medical University,Guangzhou 510000,Guangdong,China)
出处
《医学信息》
2022年第13期28-33,共6页
Journal of Medical Information
基金
广东省高水平临床重点专科(深圳市配套建设经费)资助项目(编号:SZGSP008)
深圳市医疗卫生三名工程(编号:SZSM202111012)。
