[PTCH1 promotes epithelial mesenchymal transition and epithelial cell proliferation in the pathogenesis of chronic sinusitis with nasal polyps].

Objective: To investigate the role of PTCH1 in epithelial-mesenchymal transition (EMT) and the development of chronic sinusitis with nasal polyps (CRSwNP). Methods: A total of 240 nasal polyps from CRSwNP patients were collected as experimental group, while nasal mucosa tissues from 30 patients with deviated nasal septum were collected as control group. They were all diagnosed at Beijing Chaoyang Hospital, Beijing, China from 2015 to 2023. Fifty-two CRSwNP samples were subjected to targeted next-generation sequencing. The effect of PTCH1 on the proliferation of nasal mucosal epithelial cells was detected using cell culture and the CCK8 assay. The expression of PTCH1, EMT markers (including E-cadherin, vimentin, and SMA) and the EMT-related transcription factor Snail/Slug were assessed using immunohistochemical staining. Results: Among the 240 cases of CRSwNP, 179 were male and 61 were female, with an average age of 49 (18, 72) years. Among the 30 cases of deviated nasal septum, 19 were male and 11 were female, age 42 (19, 75) years old. Targeted next-generation sequencing revealed that the mutation rate of PTCH1 in CRSwNP was 7.7% (4/52),which was significantly higher than the mutation frequency of less than 1% in the database of normal individuals. Cell culture and CCK8 assay showed that PTCH1 mutation could promote the proliferation of nasal mucosal epithelial cells. Immunohistochemical staining showed that 116 cases(116/240) CRSwNP were moderately to strongly positive for PTCH1, 114 cases (114/240) were weakly positive, and 10 cases (10/240) were negative. Two hundred and one of the 240 cases were weakly positive for E-cadherin, 4 cases (4/240) were moderately positive and 35 cases (35/240) were negative. Vimentin, SMA, Snail and Slug all showed various degrees of positive expression. Meanwhile, expression of PTCH1 was elevated in CRSwNP and correlated with the expression of Snail/Slug (r=0.776, P<0.01; r=0.767, P<0.01, respectively). Conclusions: PTCH1 mutation is an important genetic variant in CRSwNP. PTCH1 mutation activates the Hedgehog signaling pathway and promotes the EMT process by upregulating the expression of the transcription factor Snail/Slug, while PTCH1 mutation also directly promotes the proliferation of nasal mucosal epithelial cell. Both processes/pathways are involved in the development of CRSwNP and have the potential to become the targets for the future clinical therapy of CRSwNP.