基于WGCNA分析口腔鳞状细胞癌中潜在的铁死亡生物标志物和免疫细胞浸润特征  

Potential ferroptosis biomarkers and immune cell infiltration characteristics in oral squamous cell carcinoma using WGCNA analysis

作　　者：舒佳玉 王欢 陆婧 陈河林 董强 SHU Jiayu;WANG Huan;LU Jing;CHEN Helin;DONG Qiang(School of Stomatology,Guizhou Medical University,Guizhou Guiyang 550004,China;Department of Prosthodontics and Implantology,Affiliated Stomatological Hospital of Guizhou Medical University,Guizhou Guiyang 550004,China.)

机构地区：[1]贵州医科大学口腔医学院,贵州贵阳550004 [2]贵州医科大学附属口腔医院修复种植科,贵州贵阳550004

出　　处：《现代肿瘤医学》2024年第19期3636-3642,共7页Journal of Modern Oncology

基　　金：国家自然科学基金地区项目(编号:82160186)。

摘　　要：目的:筛选口腔鳞状细胞癌(OSCC)中铁死亡相关新型生物标志物,并分析免疫细胞浸润情况。方法:从GEO数据库中下载OSCC数据集。利用R软件筛选差异表达基因(DEGs)并进行功能和通路富集分析,通过加权基因共表达网络分析(WGCNA)探究基因间的相互作用模块,与DEGs取交集获取关键基因,并在临床样本中进行验证。对关键基因进行ROC分析和生存分析并利用CIBERSORT进行免疫细胞浸润分析。结果:共筛选出19个DEGs和3个关键基因(CHAC1、PGD、PTGS2),其中CHAC1和PGD在OSCC中显著下调,PTGS2显著上调,DEGs主要涉及谷胱甘肽生物合成过程、非核糖体肽生物合成过程、氧化应激反应过程、谷胱甘肽代谢过程和细胞修饰氨基酸。KEGG分析显示谷胱甘肽代谢、铁死亡和磷酸戊糖途径等信号通路明显富集。ROC分析显示CHAC1、PGD和PTGS2具有较高的诊断价值。生存分析显示,CHAC1、PGD和PTGS2在OSCC组织中的表达水平与其预后显著相关。免疫细胞浸润分析显示,初始CD4+T细胞、调节性T细胞、CD8+T细胞、中性粒细胞和树突状细胞的活化等在OSCC和正常样本中的差异表达具有统计学意义(均P<0.05)。结论:CHAC1、PGD和PTGS2可作为潜在的诊断和预后的生物标志物,初始CD4+T细胞、调节性T细胞、CD8+T细胞、中性粒细胞和树突状细胞的活化参与OSCC的发生发展,为OSCC的早期诊断、预后和分子机制研究提供一定的参考依据。Objective:To screen novel biomarkers related to ferroptosis in oral squamous cell carcinoma(OSCC)and analyze immune cell infiltration.Methods:The OSCC datasets were downloaded from the GEO database.Differentially expressed genes(DEGs)were screened by R and functional and pathway enrichment analysis was performed.The interaction modules between genes were explored by weighted gene co-expression network analysis(WGCNA),crossed with DEGs to obtain key genes and verified in clinical samples.ROC analysis and survival analysis were performed on key genes and immune cell infiltration was analyzed using CIBERSORT.Results:A total of 19 DEGs and 3 key genes(CHAC1,PGD,PTGS2)were screened out,among which CHAC1 and PGD were significantly downregulated in OSCC,while PTGS2 was significantly upregulated.DEGs were mainly involved in glutathione biosynthetic process,nonribosomal peptide biosynthetic process,response to oxidative stress process,glutathione metabolic process and cellular modified amino acid biosynthesis process.KEGG analysis showed an obvious enrichment of signaling pathways such as glutathione metabolism,ferroptosis and pentose phosphate pathway.The ROC analysis showed a high diagnostic value of PGD,CHAC1,and PTGS2.Survival analysis showed that the expression levels of CHAC1,PGD,and PTGS2 in OSCC were significantly correlated with prognosis.Immune cell infiltration analysis showed statistically significant differences in CD4+T cell,T cells regulatory(Tregs),CD8+T cells,neutrophils and dendritic cells activated(all P<0.05).Conclusion:CHAC1,PGD,and PTGS2 may serve as potential diagnostic and prognostic biomarkers.The activation of CD4+T cell,T cells regulatory(Tregs),CD8+T cells,neutrophils and dendritic cells activated participates in the occurrence and development of OSCC,providing some reference basis for the early diagnosis,prognosis and molecular mechanism study of OSCC.

关 键 词：口腔鳞状细胞癌 铁死亡 差异表达基因 加权基因共表达网络分析 免疫细胞浸润 

分 类 号：R739.8[医药卫生—肿瘤]