M2 macrophage derived HMOX1 defines chronic rhinosinusitis with nasal polyps

作者：E.D. Wang, Yanghe Hao, Jing Song, Jing Yuan, Yu Hong, Ying Li, Yang Wang, Chengshuo Wang, Ming Wang, Luo Zhang · 发表于：Clinical and Translational Allergy · 年份：2024 · DOI：10.1002/clt2.70014 · 被引用次数：11 · 研究领域：Sinusitis and nasal conditions、Allergic Rhinitis and Sensitization、Cystic Fibrosis Research Advances

BACKGROUND: Molecular signatures of chronic rhinosinusitis with nasal polyps (CRSwNP) related to macrophages remain unclear. This study aimed to develop a macrophage-associated diagnostic signature for CRSwNP. METHODS: Transcriptome data from 54 patients with CRSwNP and 37 healthy controls across GSE136825, GSE36830, and GSE72713 were used to identify differentially expressed genes (DEGs) between two groups. Gene Set Enrichment Analysis and Weighted Gene Co-Expression Network Analysis pinpointed crucial pathways and gene clusters. A diagnostic model was created from these analyses and receiver operating characteristic curve (ROC), and further validated in our transcriptome data from 29 samples. Immune cell infiltration analysis was performed and linked those diagnostic genes to macrophages and verified by single-cell RNA sequencing data. Immunofluorescence co-staining of CD163 and HMOX1 was performed in nasal tissues. Mouse bone marrow-derived macrophage (BMDMs) cultures were used in functional experiments. Correlations between the expression of HMOX1 and eotaxin genes were investigated. RESULTS: DEGs of CRSwNP versus control group were enriched in the INTERLEUKIN_4_AND_13_SIGNALING pathways. A four-gene diagnostic model (HMOX1, ALOX5, F13A1 and ITGB2) was developed and demonstrated high diagnostic precision with an area under ROC curve of 0.980 for training dataset and 0.895 for test dataset. M2 macrophage presence and HMOX1 expression significantly correlated with CRSwNP (p...