Lin Yingying, Lai Xiaofan, Lei Tianxiang, Qiu Yuan, Deng Qiwen, Liu Qi, Wang Zhongxing, Huang Wenqi
Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
J Inflamm Res. 2023 Jun 14;16:2503-2519. doi: 10.2147/JIR.S414734. eCollection 2023.
Idiopathic pulmonary fibrosis (IPF) is a disease with unclear etiology and a poor prognosis. Although the involvement of neutrophils in IPF pathogenesis has been suggested, the exact nature of this relationship remains unclear.
We analyzed data from the Gene Expression Omnibus (GEO) using immune infiltration analysis, weighted gene co-expression network analysis (WGCNA), and consensus cluster analysis. Neutrophil-related genes and hub genes related to neutrophils were identified and differentially expressed between IPF patients and healthy controls. We also validated the expression differences of hub genes in a bleomycin-induced mice model.
Immune infiltration analysis revealed a significantly decreased percentage of neutrophils in the lung tissue of IPF patients compared with healthy controls (P<0.001) in both the train and validation sets. Neutrophil-related genes in IPF were identified by WGCNA, and functional enrichment analysis showed that these genes were mainly involved in the cytokine-cytokine receptor interaction pathway and correlated with lung disease, consistent with DEGs between IPF and healthy controls. Eight hub genes related to neutrophils were identified, including , and . Consensus cluster analysis revealed a low neutrophil-infiltrating cluster that was correlated with IPF (P<0.001), and a principal component analysis-generated score could distinguish IPF patients from healthy controls, with an area under the curve of 0.930 in the train set and 0.768 in the validation set. We also constructed a diagnostic model using hub genes related to neutrophils, which showed a reliable diagnostic value with an area under the curve of 0.955 in the train set and 0.995 in the validation set.
Our findings provide evidence of a low neutrophil-infiltrating characteristic in the IPF microenvironment and identify hub genes related to neutrophils that may serve as diagnostic biomarkers for the disease.
特发性肺纤维化（IPF）是一种病因不明、预后较差的疾病。尽管有研究提示中性粒细胞参与了IPF的发病机制，但其确切关系仍不明确。
我们使用免疫浸润分析、加权基因共表达网络分析（WGCNA）和共识聚类分析，对基因表达综合数据库（GEO）的数据进行了分析。确定了中性粒细胞相关基因和与中性粒细胞相关的枢纽基因，并比较了IPF患者与健康对照之间的差异表达。我们还在博来霉素诱导的小鼠模型中验证了枢纽基因的表达差异。
免疫浸润分析显示，在训练集和验证集中，与健康对照相比，IPF患者肺组织中的中性粒细胞百分比均显著降低（P<0.001）。通过WGCNA确定了IPF中的中性粒细胞相关基因，功能富集分析表明这些基因主要参与细胞因子-细胞因子受体相互作用途径，并与肺部疾病相关，这与IPF和健康对照之间的差异表达基因一致。确定了8个与中性粒细胞相关的枢纽基因，包括 ，以及 。共识聚类分析显示，一个低中性粒细胞浸润簇与IPF相关（P<0.001），主成分分析生成的评分可以区分IPF患者与健康对照，训练集中曲线下面积为0.930，验证集中为0.768。我们还使用与中性粒细胞相关的枢纽基因构建了一个诊断模型，该模型在训练集中曲线下面积为0.955，在验证集中为0.995，显示出可靠的诊断价值。
我们的研究结果提供了证据，证明IPF微环境中存在低中性粒细胞浸润特征，并确定了与中性粒细胞相关的枢纽基因，这些基因可能作为该疾病的诊断生物标志物。
