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基于生物信息学分析慢性阻塞性肺疾病中铁死亡相关生物标志物
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Abstract:
目的：基于生物信息学分析慢性阻塞性肺疾病(chronic obstructive pulmonary disease, COPD)与铁死亡的功能富集通路以及关键基因，为COPD的预防和诊断提供新的方向。方法：通过GEO数据库获得COPD相关数据集GSE76925，筛选正常组织样本和COPD组织样本差异表达基因，从FerrDb下载铁死亡相关基因集，提取铁死亡相关基因在GSE76925数据集中的表达矩阵，获得铁死亡相关的差异表达基因，对差异基因进行GO和KEGG富集分析。通过SVM-RFE和LASSO确定COPD的特征基因，并绘制ROC曲线和计算AUC来评估特征基因的诊断效果。使用CIBERSORT对肿瘤微环境中的免疫细胞进行评估，并评估特征基因与免疫细胞浸润之间的关系。结果：得到4个铁死亡相关特征基因，NOX4、FBXW7、TIMM9、ARF6，ROC结果均显示出良好的诊断价值。特征基因与M0巨噬细胞、肥大细胞、浆细胞、树突状细胞等显著相关。结论：得到的4个关键基因NOX4、FBXW7、TIMM9、ARF6为COPD发病机制以及预防诊断提供新思路，从而指导疾病临床治疗。
Objective: Bioinformatics-based analyses of functional enrichment pathways and key genes in chronic obstructive pulmonary disease and ferroptosis to provide new directions for COPD prevention and diagnosis. Methods: The COPD-related dataset GSE76925 was obtained from the GEO database, normal tissue samples and COPD tissue samples were screened for differentially expressed genes, the ferroptosis-related gene set was downloaded from FerrDb, and the expression matrices of the ferroptosis-related genes in the GSE76925 dataset were extracted to obtain the ferroptosis-related differentially expressed genes, and the differential genes were subjected to GO and KEGG enrichment Analysis. The signature genes of COPD were identified by SVM-RFE and LASSO, and the diagnostic efficacy of the signature genes was assessed by plotting ROC curves and AUC. Assessment of immune cells in the tumor microenvironment using CIBERSORT and characterization of the relationship between genes and immune cell infiltration. Results: Four ferroptosis-related signature genes, NOX4, FBXW7, TIMM9, and ARF6, were obtained and the ROC results showed good diagnostic value. Characterized genes were significantly associated with M0 macrophages, mast cells, plasma cells and dendritic cells. Conclusions: The four key genes obtained, NOX4, FBXW7, TIMM9, and ARF6, provide new ideas for COPD pathogenesis as well as preventive diagnosis, thus guiding clinical treatment of the disease.
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