1.Screening and validation of therapeutic targets for chronic sinusitis with nasal polyps based on proteomics
Tong LI ; Caiyu SUN ; Zheying SONG ; Yujuan YANG ; Yu ZHANG ; Xicheng SONG
Chinese Journal of Otorhinolaryngology Head and Neck Surgery 2024;59(7):735-744
Objective:To identify potential therapeutic targets of chronic sinusitis with nasal polyps (CRSwNP) through proteomics screening of and verify its effectiveness experimentally.Methods:The nasal tissue samples were collected from patients undergoing surgical treatment in the Department of Otorhinolaryngology, Head and Neck Surgery in Yuhuangding Hospital of Yantai from June 2010 to December 2021, including 69 patients with CRSwNP and 39 patients in the control group. Tissue samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition (DIA) mode to find differentially expressed proteins. Bioinformatics tools were employed to analyze the functions of differentially expressed proteins. The expression of hematopoietic cell kinase (HCK) in nasal tissues of patients with CRSwNP was further confirmed by qPCR and western blot. The mouse model of CRSwNP was established and treated with HCK inhibitor. The levels of inflammatory factors IgE, IL-4 and IL-5 in serum of CRSwNP mice, both treated and untreated with HCK inhibitors, were detected by enzyme-linked immunosorbent assay (ELISA) across different experimental groups. The experimental data were analyzed by Graphpad Prism 9 software.Results:DIA analysis identified 1 850 differential proteins, including 760 up-regulated proteins and 1 090 down-regulated proteins. Weighted correlation network analysis (WGCNA) correlation analysis of phenotypic data such as cell count and CT score with the results of genomics indemnified 575 proteins of MEBrown module which intersected with 35 kinases further screened from 1 850 differential proteins, yielding eight protein kinases: HCK, SYK, PDK2, FGR, PRKCB, ROR1, CAMK1 and GRK6. qPCR showed that the expression of HCK in CRSwNP was significantly higher than that in the control group ( P<0.05). Further experiments in mice confirmed that the secretion of IgE, IL-4 and IL-5 in the serum of CRSwNP group was significantly higher than the control group (all P<0.05), indicating successful model establishment. The intervention of HCK significantly decreased the secretion of IgE, IL-4 and IL-5 in serum of mice (all P<0.05). Conclusion:The HCK inhibitor can reduce the inflammatory index of mice with CRSwNP, and HCK is a potential therapeutic target of CRSwNP.
2.The analysis of independent factors affecting tissue inflammatory cells changes in recurrent nasal polyps
Zheying SONG ; Jianwei WANG ; Xianghuang LUO ; Yujuan YANG ; Yu ZHANG ; Xicheng SONG
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(2):109-112
OBJECTIVE To explore the independent factors affecting tissue inflammatory cells changes in recurrent nasal polyps.METHODS The clinical data of 31 patients with nasal polyps who underwent endoscopic surgery at the Department of Otolaryngology Head and Neck Surgery,Yantai Yuhuanding Hospital from December 2007 to December 2021 were selected and analyzed by stepwise regression logistic analysis.RESULTS The number of tissue inflammatory cells in recurrent nasal polyps changed compared with that in primary nasal polyps,and the number and percentage of neutrophils in recurrent polyps increased(P<0.05).Logistic analysis revealed that smoking was an independent risk factor for eosinophilia in recurrent nasal polyps,increasing age was an independent factor for lowering neutrophils,and the comorbid allergic rhinitis and the time interval of recurrence were independent factors for lowering and increasing lymphocytes,respectively.CONCLUSION The number of tissue-infiltrating cells is altered in recurrent polyps compared with primary polyps.Smoking is an independent risk factor for eosinophilia in recurrent polyps.