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M2 macrophage-related gene signature in chronic rhinosinusitis with nasal polyps
Ying Zhu1,2,3, Xiwen Sun1,2,3, Shaolin Tan1,2,3
1Department of Otolaryngology-Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background:
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common sinonasal inflammatory disorder with high heterogeneity. Increasing evidence have indicated that the infiltration of macrophages especially M2 macrophages play pivotal roles in the pathogenesis of CRSwNP, but the underlying mechanisms remain undetermined. This study sought to identify potential biomarkers related to M2 macrophages in CRSwNP.
Methods:
The expression datasets of GSE136825 and GSE179265 were download from Gene Expression Omnibus (GEO) database and merged. Then, CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were applied to identify M2 macrophage-related gene modules. Thereafter, differentially expressed genes (DEGs) related to M2 macrophages were selected to perform functional enrichment analyses. A protein-protein interaction (PPI) network was built to identify hub genes and quantitative real-time reverse transcriptions PCR was used to verify the bioinformatics results.
Results:
A total of 92 DEGs associated with M2 macrophages were identified for further analysis. The results of Gene ontology (GO) and Kyoto Encyclopedia of genes and genomes (KEGG) analyses illustrated that M2 macrophage-associated DEGs primarily enriched in immune responses and extracellular matrix structure. PPI network analysis identified 18 hub genes related to M2 macrophages that might be pivotal in the pathogenesis of CRSwNP. After verification, AIF1, C1QA, C1QB, C3AR1, CCR1, CD163, CD4, CD53, CD86, CSF1R, CYBB, FCER1G, FCGR3A, IL10RA, ITGB2, LAPTM5, PLEK, TYROBP were identified as potential M2 macrophage-related biomarkers for CRSwNP.
Conclusion:
These findings yield new insights into the hub genes and mechanisms related to M2 macrophages in the pathogenesis of CRSwNP. Further studies of these hub genes would help better understand the disease progression and identify potential treatment targets.
Insights
This study identifies key M2 macrophage biomarkers for chronic rhinosinusitis with nasal polyps (CRSwNP). These findings offer insights into CRSwNP pathogenesis and potential therapeutic targets.
Area of Science:
- Immunology
- Genomics
- Bioinformatics
Background:
- Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous inflammatory disorder.
- M2 macrophages are implicated in CRSwNP pathogenesis, but mechanisms are unclear.
- This study aimed to find M2 macrophage-related biomarkers in CRSwNP.
Purpose of the Study:
- Identify potential biomarkers associated with M2 macrophages in CRSwNP.
- Elucidate the role of M2 macrophages in the disease's inflammatory pathways.
- Discover novel therapeutic targets for CRSwNP.
Main Methods:
- Integrated gene expression datasets (GSE136825, GSE179265) from the GEO database.
- Applied CIBERSORT and WGCNA to identify M2 macrophage-related gene modules.
- Utilized DEG analysis, GO/KEGG enrichment, PPI networks, and qRT-PCR for validation.
Main Results:
- Identified 92 M2 macrophage-associated DEGs.
- Enrichment analyses showed involvement in immune responses and extracellular matrix.
- Discovered 18 hub genes, with 18 validated as potential CRSwNP biomarkers (e.g., AIF1, CD163, CSF1R).
Conclusions:
- Identified novel M2 macrophage-related hub genes crucial for CRSwNP pathogenesis.
- These biomarkers provide insights into disease mechanisms.
- Further research on these genes may lead to new treatment strategies for CRSwNP.
