Identification and experimental validation of biomarkers associated with integrative stress response in chronic rhinosinusitis with nasal polyps

Background Chronic rhinosinusitis with nasal polyps(CRSwNP) is a persistent inflammatory disease affecting the nasal and sinus mucosa, marked by the development of polyps within the nasal passages. Certain inflammatory conditionshave the ability to trigger stress response pathways inside cells. We set out to find out what role biomarkers of the integrated stress response(ISR) may play in CRSwNP. Methods The study obtained data pertaining to the transcriptome of CRSwNP and genes associated with ISR from public database and literature, respectively. Bioinformatics techniques, including expression validation, machine learning, and differential expression analysis, were used to identify biomarkers linked to ISR in CRSwNP. Subsequently, we investigated the role of these biomarkers in the regulatory pathways of CRSwNP through functional enrichment studies, immune cell infiltration evaluation, and construction of regulatory networks. Finally,RT-qPCR was employed to validate the expression levels of identified biomarkers in patient-derived specimens. Results CYBB, EGLN3, HMOX1, and TGFB1 were identified as biomarkers for CRSwNP. Interestingly, CYBB, EGLN3, and HMOX1 were found to be co-enriched in the pathway of “natural killercell-mediated cytotoxicity”. Furthermore, 23 DICs were discerned between the CRSwNP and control groups. It was noteworthy that CYBB and HMOX1 exhibited a pronounced inverse correlation with type 2 T helper cell and a positive correlation with the remaining 22 DICs. Notably, the expression of CYBB and EGLN3 was found to be regulated by multiple factors, including 29 miRNAs(such as hsa-miR-373a-3p)and seven ncRNAs(like SNHG16). Additionally, SPI1 served as a common TF for CYBB, EGLN3, HMOX1, and TGFB1. Finally, the RT-qPCR analysis indicated a significant elevation in the expression levels of CYBB, EGLN3, HMOX1, and TGFB1 within the CRSwNP group(P < 0.05). Conclusion This study identified four effective biomarkers for CRSwNP,thereby providing potential therapeutic targets for CRSwNP patients.