| Objective:Compared with chronic rhinosinusitis with nasal polyps(CRSwNP)without asthma,patients with CRSwNP and asthma comorbidity(ACRSwNP)have more severe clinical symptoms,are more difficult to treat,and are more likely to relapse after surgery.This study used the transcriptome data of ACRSwNP and asthma in the public database,explored the transcriptome characteristics of ACRSwNP by combining the upper and lower airway gene expression data of asthma patients,and clarified the mechanism of ACRSwNP at the level of transcriptomics,to formulate a more effective treatment plan for ACRSwNP provide a theoretical basis.Methods:The ACRSwNP and asthma datasets were downloaded from the GEO database.R software was used to determine ACRSwNP-related differentially expressed genes(DEGs)and combined with weighted gene coexpression network analysis(WGCNA)to screen hub genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed on hub genes.The co-expressed genes of ACRSwNP and asthma were screened by analyzing upper airway DEGs of asthmatic patients.Samples from 72 patients attending the department of otolaryngology were collected for RT-PCR assay to determine the expression levels of co-expressed genes among the ACRSwNP group,CRSwNP group,and control group.Patients were grouped according to postoperative disease control state and the factors of difference between groups were compared.The potential effect of inhaled corticosteroids(ICS)on co-expressed genes was explored using GSE89809.R and GraphPad Prism software was used for statistical analysis in this study.Results:Compared with the control group,a total of 36 hub genes were differentially expressed in nasal polyps and surrounding mucosa in ACRSwNP.GO and KEGG results showed that the hub genes were mainly related to immune response regulation,inflammatory response,the interaction between viral proteins and cytokine receptors,complement and coagulation cascade reactions,and chemokine-related signaling pathways.The co-expressed gene CST1 was upregulated in the nasal polyps and nasal mucosa of ACRSwNP and was also upregulated in the upper and lower airways of asthmatic patients.In ACRSwNP,CST1 expression level was positively correlated with IL5RA,and in asthma,CST1 had excellent diagnostic efficiency for Th2-high asthma.The RT-PCR results of the samples showed that compared with the control group,the expression of CST1 mRNA was upregulated in ACRSwNP and CRSwNP nasal polyps,and the expression level of the ACRSwNP group was higher than that of the CRSwNP group,and the difference was statistically significant.ROC curves showed that the expression level of CST1 in nasal polyps had a superior diagnostic efficiency for CRSwNP with or without asthma.The follow-up results showed that compared with CRSwNP patients,ACRSwNP patients were more difficult to maintain a postoperative control state of illness,and the expression level of CST1 in the uncontrolled group was higher than that in the controlled group.CST1 expression level has a certain predictive ability for postoperative disease control state.GSE89809 data showed that ICS could down-regulate the expression of CST1 in the bronchial epithelium of asthmatic patients.Conclusion:The up-regulation of CST1 is involved in the pathogenic mechanism of ACRSwNP,and CST1 is associated with type 2 inflammation in the upper and lower airways.Compared with CRSwNP,ACRSwNP has a higher level of CST1 expression in nasal polyps,and the CST1 expression level has a certain predictive ability for the postoperative control state of illness.High expression of CST1 may lead to a more difficult-to-control postoperative state of illness.ICS can reduce the expression level of CST1 in the bronchial epithelium of asthmatic patients,and the expression level of CST1 is negatively correlated with the dose of ICS.The high expression of CST1 plays an important role in the clinical characteristics of ACRSwNP and has the potential to be a key target for the treatment of ACRSwNP. |
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