Identification of CD14 as a Potential Biomarker Relating to PANoptosis in Chronic Obstructive Pulmonary Disease

Xue Fu,1 Jiawei Dong,2 Jian Yang,2 Xiaotian Zhang,2 Shangkun Cai,2 Yiwei Zhang,2 Shenglong Lv,2 Meng Zhang2 1Department of Emergency, Hebei Medical University Third Hospital, Shijiazhuang, 050051, People’s Republic of China; 2Department of Thoracic Surgery, Hebei Medical University Third Hospital, Shijiazhuang, 050051, People’s Republic of ChinaCorrespondence: Meng Zhang, Department of Thoracic Surgery, Hebei Medical University Third Hospital, No. 139 Ziqiang Road, Qiaoxi District, Shijiazhuang, 050051, People’s Republic of China, Email 38000435@hebmu.edu.cnBackground: The processes of pyroptosis, apoptosis, and necroptosis (PANoptosis) play a crucial role in the development of chronic obstructive pulmonary disease (COPD). Our objective is to explore potential PANoptosis-related genes in COPD.Methods: Human COPD-related transcriptomic datasets (GSE8545, GSE20257, GSE11784 and GSE1650) were retrieved from the Gene Expression Omnibus (GEO). First, based on GSE8545 dataset, candidate genes were identified using differentially expressed gene (DEG) analysis, Weighted Gene Co-expression Network Analysis (WGCNA), Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for the relevant genes. CD14 was identified as a diagnostic biomarker through validation across independent human cohorts (GSE20257 and GSE11784). CIBERSORT was employed to evaluate immune infiltration differences between CD14 expression groups. Finally, potential therapeutic drugs for CD14 were predicted using the Drug-Gene Interaction Database (DGIdb).Results: Three PANoptosis-related hub genes (CD14, IRF2, and BOK) were defined in this study. KEGG enrichment analysis revealed that these genes were significantly enriched in the “Apoptosis - multiple species” signaling pathway. Validation across multiple independent human datasets identified CD14 as the key gene. CD14 exhibited significantly elevated expression in the lung tissues of COPD patients (P < 0.001). Immune infiltration analysis indicated that CD14 expression levels were significantly negatively correlated with resting mast cells and positively correlated with monocytes. Receiver Operating Characteristic curve analysis confirmed the robust diagnostic performance and stability of CD14, with Area Under the Curve values of 0.756, 0.702, 0.703, and 0.732 in the GSE8545, GSE20257, GSE11784, and GSE1650 datasets, respectively. Furthermore, three potential therapeutic agents targeting CD14—VB-201, LOVASTATIN, and IC143—were predicted.Conclusion: We identified CD14 as a marker gene associating with PANoptosis in COPD, providing new ideas for clinical diagnosis and drug design of COPD.Keywords: COPD, PANoptosis, immune infiltration, target drugs, CD14