口腔鳞状细胞癌预后标志物的筛选及与免疫浸润的相关性分析  

Screening of prognostic biomarkers of oral squamous cell carcinoma and their correlation with immune infiltration

作　　者：刘鹏飞 辛璐 李杨[3] 刘乔 LIU Pengfei;XIN Lu;LI Yang;LIU Qiao(Department of Stomatology,Xi'an No.3 Hospital,Xi'an 710005,China;Department of Stomatology,Xi'an Honghui Hospital Yanliang Branch,Xi'an 710089,China;College of Animal Science and Technology,Northwest Agriculture and Forestry University,Yangling 712199,China;Department of Pathology,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China)

机构地区：[1]西安市第三医院口腔科,陕西西安710005 [2]西安市红会医院阎良院区口腔科,陕西西安710089 [3]西北农林科技大学动物科技学院,陕西杨凌712199 [4]空军军医大学唐都医院病理科,陕西西安710038

出　　处：《空军军医大学学报》2024年第10期1110-1118,共9页Journal of Air Force Medical University

基　　金：陕西省重点研发计划一般项目(2023-YBSF-565)。

摘　　要：目的旨在通过整合多个数据集筛选口腔鳞状细胞癌(OSCC)中预后生物标志物,并研究其与免疫浸润的相关性。方法从基因表达综合数据库(GEO)平台中提取OSCC相关数据集GSE9844、GSE30784和GSE138206。鉴定差异表达重叠基因群(DEGs),对DEGs进行基因本体论(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析,以评估DEGs参与的潜在分子过程和通路;使用STRING网站构建蛋白质与蛋白质相互作用网络图谱;使用Cytoscape软件中MCODE插件识别HUB基因;提取癌症基因组图谱网站中OSCC的表达谱数据,使用R语言工具检测HUB基因的表达情况。绘制受试者工作特征(ROC)曲线,预测正常和肿瘤组织中关键核心基因的诊断效率;使用R软件包完成HUB在OSCC免疫微环境中的表达及与24种免疫细胞的相关性分析。结果3个数据集共鉴定出231个DEGs,包括173个上调的DEGs和58个下调的DEGs。GO功能注释分析表明,DEGs主要富集在细胞外基质形成、病毒防御反应和Ⅰ型干扰素信号通路等过程。KEGG通路富集分析结果表明,DEGs主要参与细胞外基质受体相互作用、变形虫感染、小细胞肺癌、局灶黏连、PI3K-Akt信号通路和人乳头状瘤病毒感染等重要信号通路。MCODE插件计算出最大的HUB集合,包括18个HUB基因,其中只有DDX60、XAF1、ISG15和IFIT1具备成为OSCC预后标志物的潜力。DDX60的高表达提示较差的预后,而XAF1、ISG15和IFIT1的高表达则提示患者预后较好。ROC分析结果显示,DDX60、XAF1、ISG15和IFIT1在预测肿瘤和非肿瘤方面具有一定的准确性,其中ISG15具有非常高的诊断准确性。ISG15与N分期和性别显著相关,而XAF1高表达组和低表达组在性别和吸烟方面存在显著差异,其中性别最为显著(P<0.001)。DDX60、XAF1、ISG15和IFIT1的表达与OSCC免疫微环境中大多数免疫细胞的表达正相关。结论本研究从公共GEO数据库中挖掘了OSCC潜在生物标志物组Objective To screen prognostic biomarkers in oral squamous cell carcinoma(OSCC)by integrating multiple datasets and to investigate their correlation with immune infiltration.Methods We extracted OSCC-related datasets GSE9844,GSE30784,and GSE138206 from the Gene Expression Omnibus(GEO)platform,and identified differentially expressed genes(DEGs).The DEGs were then subjected to Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis to evaluate their potential molecular processes and pathways.STRING website was used to construct a protein-protein interaction network and MCODE plug-in of the Cytoscape software to identify HUB genes.The expression profile data of OSCC were extracted from The Cancer Genome Atlas website,and R tools were used to examine the expression of HUB genes.Receiver operating characteristic(ROC)curves were plotted to predict the diagnostic efficiency of key core genes in both normal and tumor tissues.R software package was used to analyze the expression of HUB genes in OSCC immune microenvironment and their correlation with 24 types of immune cells.Results A total of 231 DEGs were identified in the three datasets,including 173 upregulated DEGs and 58 downregulated DEGs.GO functional annotation analysis showed that DEGs were mainly enriched in the formation of extracellular matrix,virus defense response,typeⅠinterferon signal pathways,and other processes.The results of KEGG pathway enrichment analysis showed that DEGs were mainly involved in extracellular matrix receptor interaction,amoeba infection,small cell lung cancer,focal adhesion,PI3K-Akt signal pathway,human papilloma virus infection,and other important signal pathways.MCODE plug-in calculated the largest set of HUB genes,including 18 HUB genes,of which only DDX60,XAF1,ISG15,and IFIT1 had the potential to be prognostic biomarkers for OSCC.High expression of DDX60 suggested a poor prognosis,while high expression of XAF1,ISG15,and IFIT1 suggested a good prognosis.ROC analysis resu

关 键 词：口腔鳞状细胞癌 DDX60 XAF1 ISG15 IFIT1 免疫浸润 

分 类 号：R739[医药卫生—肿瘤]