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作 者:尚多[1] 武旭 周兴安 苏尼特 德乐黑巴特尔 申铁兵[1] SHANG Duo;WU Xu;ZHOU Xing’an;Sunite;Deleheibateer;SHEN Tiebing(Department of Stomatology,The Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,China;Department of Oral Surgery,Hohhot Stomatological Hospital,Hohhot 010031,China)
机构地区:[1]内蒙古医科大学附属医院口腔科,内蒙古呼和浩特010050 [2]呼和浩特市口腔医院口腔外科,内蒙古呼和浩特010031
出 处:《内蒙古师范大学学报(自然科学版)》2025年第2期111-119,共9页Journal of Inner Mongolia Normal University(Natural Science Edition)
基 金:内蒙古自治区自然科学基金资助项目“LncRNA GSEC竞争性结合miR-144调控CXCL8在口腔鳞癌中的作用及机制研究”(2024QN08053);内蒙古自治区高等学校科学研究资助项目“数字化导板辅助精确治疗颧眶骨折的临床研究”(NJZY21634);内蒙古医科大学联合资助项目“血清外泌体circRNA在口腔鳞癌中的差异性表达及其功能的研究”(YKD2023LH032)。
摘 要:采用生物信息学方法探索与头颈鳞状细胞癌(headandnecksquamouscellcarcinoma,HNSCC)组织中铁死亡相关的基因,并探讨其与免疫细胞浸润及患者预后的相关性,为HNSCC患者提供新的分子靶点。通过GEO数据库检索筛选得到基因微阵列数据集GSE228393,对GSE228393数据集进行GEO2R分析获得差异表达基因;通过TCGA获取HNSCC的高通量测序数据,利用R语言进行差异分析,利用FerrDb数据库检索得到铁死亡相关基因与GSE228393及TCGA数据库差异基因取交集,对交集基因进行GO与KEGG功能富集分析获取相关信号通路,并进行蛋白互作分析、生存分析以及免疫浸润分析。结果表明,有6个铁死亡相关基因FADS1、CA9、PDK4、IDO1、NOX4、AR在数据集中差异表达,且与HNSCC患者的总生存期(overall survival,OS)及免疫细胞浸润密切相关;功能富集分析表明基因功能主要富集在细胞程序性死亡的正向调控;KEGG通路主要富集在HIF-1信号通路;差异表达的基因在HNSCC中有一定突变率。基于肿瘤生物信息学的分析发现,铁死亡相关基因在HNSCC组织中的表达水平与正常组织有差异,且表达水平与免疫细胞浸润及肿瘤预后具有相关性,可作为HNSCC预后标志物以及基因治疗靶点。This study explored the ferroptosis-related genes in head and neck squamous cell carcinoma(HNSCC)tissues with the help of bioinformatics and investigated their correlation with immune cell infiltration and patient prognosis,aiming to provide new molecular targets for HNSCC patients.The gene microarray dataset GSE228393 was obtained through retrieval and screening on the GEO database and then subjected to GEO2R analysis to make clear differential expression genes.High-throughput sequencing data of HNSCC were obtained from TCGA,and differential analysis was conducted using R language.Ferroptosis-related genes were retrieved from the FerrDb database,and the intersection was determined for their differential genes with GSE228393 and the TCGA database.GO and KEGG functional enrichment analyses were performed on the common genes to obtain relevant signaling pathways,followed by protein-protein interaction analysis,survival analysis,and immune infiltration analysis.The results showed that six ferroptosis-related genes,namely FADS1,CA9,PDK4,IDO1,NOX4,and AR,were differentially expressed in the dataset and closely related to the overall survival(OS)and immune cell infiltration in HNSCC patients.Functional enrichment analyses revealed that the gene functions were mainly enriched in the positive regulation of programmed cell death.The KEGG pathways were mainly enriched in the HIF-1 signaling pathway.The differentially expressed genes had a certain mutation rate in HNSCC.Based on tumor bioinformatics analysis,the study found that the expression levels of ferroptosis-related genes in HNSCC tissues differed from those in normal tissues,and their expression levels were correlated with immune cell infiltration and tumor prognosis.Therefore,they can serve as prognostic markers and gene therapy targets for HNSCC.
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