Huang Xiangfei, Yu Wen, Tian Juan, Zhang Yang, Wei Aiping, Li Yong, Chen Shibiao
Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China.
Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi 330006, PR China.
Gene. 2025 Jul 10;956:149464. doi: 10.1016/j.gene.2025.149464. Epub 2025 Apr 3.
Idiopathic pulmonary fibrosis (IPF) is a progressive lung disorder that is characterized by the disruption of lung architecture and respiratory failure. Notwithstanding the advent of novel therapeutic agents such as pirfenidone and nintedanib, there remains a pressing need for the development of innovative diagnostic and therapeutic strategies. Next-generation sequencing allows for the analysis of gene expression and the discovery of biomarkers. The objective of our study was to identify IPF-specific gene signatures, construct a diagnostic nomogram, and explore the role of the extracellular matrix (ECM) and epithelial-to-mesenchymal transition (EMT) in IPF pathogenesis. Utilizing data from the Gene Expression Omnibus (GEO) database, we identified differentially expressed genes (DEGs), performed weighted correlation network analysis (WGCNA), and constructed a nomogram. The present study has identified a group of key genes that are associated with IPF. The identified genes include GREM1, ITLN2, MAP3K15, RGS9BP, and SLCO1A2. The results of the immunohistochemical analysis indicated a significant correlation between these central genes and immune cell infiltration. Furthermore, Gene Set Enrichment Analysis (GSEA) revealed that these genes play a critical role in the pathogenesis of IPF. To validate the diagnostic potential of these core genes, we performed confirmatory analyses in independent Gene Expression Omnibus (GEO) datasets. We observed a significant upregulation of GREM1 expression in IPF animal and cellular models. These findings provide new insights into the molecular mechanisms of IPF and suggest potential targets for future diagnostic and therapeutic strategies.
特发性肺纤维化（IPF）是一种进行性肺部疾病，其特征是肺结构破坏和呼吸衰竭。尽管出现了诸如吡非尼酮和尼达尼布等新型治疗药物，但仍迫切需要开发创新的诊断和治疗策略。下一代测序允许分析基因表达并发现生物标志物。我们研究的目的是识别IPF特异性基因特征，构建诊断列线图，并探讨细胞外基质（ECM）和上皮-间质转化（EMT）在IPF发病机制中的作用。利用来自基因表达综合数据库（GEO）的数据，我们识别了差异表达基因（DEG），进行了加权相关网络分析（WGCNA），并构建了列线图。本研究确定了一组与IPF相关的关键基因。所识别的基因包括GREM1、ITLN2、MAP3K15、RGS9BP和SLCO1A2。免疫组织化学分析结果表明这些核心基因与免疫细胞浸润之间存在显著相关性。此外，基因集富集分析（GSEA）显示这些基因在IPF发病机制中起关键作用。为了验证这些核心基因的诊断潜力，我们在独立的基因表达综合数据库（GEO）数据集中进行了验证分析。我们观察到GREM1在IPF动物和细胞模型中的表达显著上调。这些发现为IPF的分子机制提供了新的见解，并为未来的诊断和治疗策略提出了潜在靶点。
