基于加权基因共表达网络探索喉癌干性关键基因  

Identification of stemness-related genes in laryngeal cancer by weighted gene co-expression network analysis

作　　者：昝雨欣 丁妍[2,3] ZAN Yuxin;DING Yan(Institute of Biological Medicine,Hubei University of Medicine,Shiyan 442000,Hubei Province,China;Instiute of Life Sciences,Taihe Hospital,Affiliated Hospital of Hubei University of Medicine,Shiyan 442000,Hubei Province,China;Hubei Key Laboratory of Embryonic Stem Cell Research,Shiyan 442000,Hubei Province,China)

机构地区：[1]湖北医药学院生物医药研究院,湖北十堰442000 [2]湖北医药学院附属太和医院生命科学研究所,湖北十堰442000 [3]胚胎干细胞研究湖北省重点实验室,湖北十堰442000

出　　处：《数理医药学杂志》2024年第3期171-179,共9页Journal of Mathematical Medicine

摘　　要：目的采用肿瘤干性指数mRNAsi筛选喉癌相关基因,为喉癌相关研究提供新思路。方法从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库下载喉癌mRNA表达谱,采用加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)构建基因共表达网络模块,得到干性最显著模块的差异表达基因。采用Cox回归和最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)算法建立风险曲线,基于肿瘤免疫功能障碍与排斥(Tumor Immune Dysfunction and Exclusion,TIDE)数据库采用单样本基因集富集分析(single sample gene set enrichment analysis,ssGSEA)探索交集基因的免疫浸润模式,基于CellMiner数据库分析基因药物敏感性,运用基因集富集分析(gene set enrichment analysis,GSEA)富集关键基因在喉癌所参与的功能和信号通路。结果通过WGCNA共构建30个喉癌共表达基因模块,选择浅黄色和紫色共表达基因模块进行Cox回归分析。LASSO算法构建模型筛选得到MTHFD2和TBX2基因,并构建风险曲线,其与浆细胞样树突状细胞(plasmacytoid dendritic cells,pDCs)和辅助性T细胞2(T helper 2 cell,Th2)免疫细胞相关,且低风险组的TIDE评分明显高于高风险组,达沙替尼与基因耐药性增加相关,功能富集显示关键基因可能与角化细胞相关。结论MTHFD2和TBX2基因可作为喉癌mRNAsi相关生物标志物。Objective To screen genes associated with laryngeal cancer using tumor stemness index(mRNAsi),in order to provide new ideas for laryngeal cancer research.Methods Laryngeal cancer mRNA expression profile was downloaded from The Cancer Genome Atlas(TCGA)database,weighted gene co-expression network analysis(WGCNA)was used to construct gene co-expression network module,and the differential genes of the most significant dry module were obtained.Cox regression and least absolute shrinkage and selection operator(LASSO)algorithms were used to establish risk curves,single sample gene set enrichment analysis(ssGSEA)was then used to explore the immune infiltration pattern of intersected genes based on Tumor Immune Dysfunction and Exclusion(TIDE)database,and CellMiner database was used to analyze gene drug sensitivity.Gene set enrichment analysis(GSEA)was used to enrich the functions and signaling pathways of key genes involved in laryngeal cancer.Results A total of 30 laryngeal cancer co-expression gene modules were constructed by WGCNA,and the light yellow and purple co-expression modules were selected for Cox regression analysis.LASSO algorithm constructed a model to screen MTHFD2 and TBX2 genes,and constructed a risk curve,which were associated with plasmacytoid dendritic cell precursors(pDCs)and T helper 2 cell(Th2)immune cells.TIDE in low-risk group was significantly higher than that in high-risk group,and dasatinib was associated with increased gene resistance.Functional enrichment showed that key genes may be related to keratinocytes.Conclusion MTHFD2 and TBX2 genes can be used as biomarkers of laryngeal cancer mRNAsi.

关 键 词：喉癌 肿瘤干细胞 干性指数 免疫 加权基因共表达网络分析 

分 类 号：R739.65[医药卫生—肿瘤]