Department of Pulmonary and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Respiration, The First Hospital of Harbin, Harbin, China.
Medicine (Baltimore). 2024 Jan 12;103(2):e36801. doi: 10.1097/MD.0000000000036801.
Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with clinical and pathological heterogeneity. Recent studies have identified cuproptosis as a novel cell death mechanism. However, the role of cuproptosis-related genes in the pathogenesis of IPF is still unclear. Two IPF datasets of the Gene Expression Omnibus database were studied. Mann-Whitney U test, correlation analysis, functional enrichment analyses, single-sample gene set enrichment analysis, CIBERSORT, unsupervised clustering, weighted gene co-expression network analysis, and receiver operating characteristic curve analysis were used to conduct our research. The dysregulated cuproptosis-related genes and immune responses were identified between IPF patients and controls. Two cuproptosis-related molecular clusters were established in IPF, the high immune score group (C1) and the low immune score group (C2). Significant heterogeneity in immunity between clusters was revealed by functional analyses results. The module genes with the strongest correlation to the 2 clusters were identified by weighted gene co-expression network analysis results. Seven hub genes were found using the Cytoscape software. Ultimately, 2 validated diagnostic biomarkers of IPF, CDKN2A and NEDD4, were obtained. Subsequently, the results were validated in GSE47460. Our investigation illustrates that CDKN2A and NEDD4 may be valid biomarkers that were useful for IPF diagnosis and copper-related clustering.
特发性肺纤维化（IPF）是一种具有临床和病理异质性的进行性致命性肺部疾病。最近的研究已经确定铜死亡是一种新的细胞死亡机制。然而，铜死亡相关基因在 IPF 发病机制中的作用仍不清楚。我们研究了两个基因表达综合数据库中的 IPF 数据集。采用曼-惠特尼 U 检验、相关分析、功能富集分析、单样本基因集富集分析、CIBERSORT、无监督聚类、加权基因共表达网络分析和接收者操作特征曲线分析进行研究。鉴定了 IPF 患者和对照之间失调的铜死亡相关基因和免疫反应。在 IPF 中建立了两个铜死亡相关的分子簇，高免疫评分组（C1）和低免疫评分组（C2）。功能分析结果揭示了簇间免疫的显著异质性。通过加权基因共表达网络分析结果鉴定了与 2 个簇相关性最强的模块基因。使用 Cytoscape 软件发现了 7 个枢纽基因。最终获得了 2 个经过验证的 IPF 诊断生物标志物，CDKN2A 和 NEDD4。随后在 GSE47460 中进行了验证。我们的研究表明，CDKN2A 和 NEDD4 可能是有效的生物标志物，可用于 IPF 诊断和铜相关聚类。
