Identification and Validation of Biomarkers in Chronic Rhinosinusitis With Nasal Polyps and Study of Their Associated Mechanisms

ABSTRACT Background Cell senescence (CS) and lipid metabolism (LM) disorders have been reported in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the mechanism is still unclear. Methods Data were obtained from public databases; differential expression analysis and machine learning were performed to identify biomarkers and to understand the pathways in which it involved. Subsequently, immune infiltration analysis was performed to observe alterations in the CRSwNP immune microenvironment. Additionally, founded on single cell data, clustering and annotation were performed to acquire key cells for pseudo‐time analysis, and to understand the interactions between different cells. Finally, reverse transcription quantitative PCR (RT‐qPCR) and immunofluorescence (IF) staining were performed to further validate the results. Results The biomarkers VDR, CPT1C, and PLA2G2A were distinguished. Notably, the VDR was primarily associated with the neutrophil extracellular trap formation pathway, suggesting a correlation with CRSwNP pathology. Next, the immune microenvironment was altered in CRSwNP patients; in total, seven cell types were annotated for the band, with monocytes and epithelial cells being the key cells. Interestingly, with the differentiation of monocytes and epithelial cells, the expression level of VDR gradually increased. Moreover, epithelial cells had the most frequent and strongest interactions with other cells, followed by monocytes. Finally, the observed expression trends of the VDR and PLA2G2A were consistent with the results of the bioinformatics analyses; however, the opposite was true for the CPT1C mRNA. Conclusion The three CRSwNP‐related biomarkers (VDR, CPT1C, PLA2G2A) associated with CS and LM were acquired, supplying novel targets for clinical diagnosis and treatment of CRSwNP.