Yang Changqing, Wang Guixin, Zhan Wenyu, Wang Yubao, Feng Jing
Respiratory Department, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Institute of Urology, Second Hospital of Tianjin Medical University, Tianjin, China.
Front Pharmacol. 2023 May 18;14:1173961. doi: 10.3389/fphar.2023.1173961. eCollection 2023.
Idiopathic pulmonary fibrosis (IPF) is caused by aberrant repair because of alveolar epithelial injury and can only be effectively treated with several compounds. Several metabolism-related biomolecular processes were found to be involved in IPF. We aimed to identify IPF subtypes based on metabolism-related pathways and explore potential drugs for each subtype. Gene profiles and clinical information were obtained from the Gene Expression Omnibus (GEO) database (GSE70867 and GSE93606). The enrichment scores for 41 metabolism-related pathways, immune cells, and immune pathways were calculated using the Gene Set Variation Analysis (GSVA) package. The ConsensusClusterPlus package was used to cluster samples. Novel modules and hub genes were identified using weighted correlation network analysis (WGCNA). Receiver operating characteristic (ROC) and calibration curves were plotted, and decision curve analysis (DCA) were performed to evaluate the model in the training and validation cohorts. A connectivity map was used as a drug probe. Two subtypes with significant differences in prognosis were identified based on the metabolism-related pathways. Subtype C1 had a poor prognosis, low metabolic levels, and a unique immune signature. CDS2, LCLAT1, GPD1L, AGPAT1, ALDH3A1, LAP3, ADH5, AHCYL2, and MDH1 were used to distinguish between the two subtypes. Finally, subtype-specific drugs, which can potentially treat IPF, were identified. The aberrant activation of metabolism-related pathways contributes to differential prognoses in patients with IPF. Collectively, our findings provide novel mechanistic insights into subtyping IPF based on the metabolism-related pathway and potential treatments, which would help clinicians provide subtype-specific individualized therapeutic management to patients.
特发性肺纤维化（IPF）是由肺泡上皮损伤导致的异常修复引起的，并且只能用几种化合物进行有效治疗。发现几种与代谢相关的生物分子过程与IPF有关。我们旨在基于与代谢相关的途径识别IPF亚型，并探索每种亚型的潜在药物。从基因表达综合数据库（GEO）（GSE70867和GSE93606）中获取基因谱和临床信息。使用基因集变异分析（GSVA）软件包计算41种与代谢相关的途径、免疫细胞和免疫途径的富集分数。使用ConsensusClusterPlus软件包对样本进行聚类。使用加权相关网络分析（WGCNA）识别新的模块和枢纽基因。绘制受试者工作特征（ROC）曲线和校准曲线，并进行决策曲线分析（DCA）以评估训练和验证队列中的模型。使用连通性图谱作为药物探针。基于与代谢相关的途径识别出两种预后有显著差异的亚型。C1亚型预后较差，代谢水平较低，且具有独特的免疫特征。使用CDS2、LCLAT1、GPD1L、AGPAT1、ALDH3A1、LAP3、ADH5、AHCYL2和MDH1来区分这两种亚型。最后，确定了可能治疗IPF的亚型特异性药物。与代谢相关途径的异常激活导致IPF患者的预后差异。总体而言，我们的研究结果为基于与代谢相关的途径对IPF进行亚型分类和潜在治疗提供了新的机制见解，这将有助于临床医生为患者提供亚型特异性的个体化治疗管理。
