Relationship between clinicopathological characteristics and CYLD expression in patients with cholesteatoma.

Shunsuke Miyake,Hirofumi Jono,Haruki Saito,Yorihisa Orita,Ayumi Kanemaru,Go Yoneda,Toru Miwa,Ryosei Minoda,Hideyuki Saito,Ramin Massoumi

doi:10.1371/journal.pone.0240216

Abstract

Middle ear cholesteatoma is a destructive disease in which inflammation plays an important role in development and progression, and there are currently no biomarkers predicting prognosis or recurrence. Cylindromatosis (CYLD), a tumor suppressor deubiquitinase, serves as a negative regulator of inflammation expressed in tissues including the middle ear. To determine the clinical significance of CYLD in acquired cholesteatoma, we evaluated CYLD expression in acquired cholesteatoma tissue by immunostaining and analyzed its correlation with clinicopathological characteristics. Our immunohistochemical analysis revealed that CYLD expression levels were varied in the tissues of acquired cholesteatoma patients. The relative expression levels of CYLD in cholesteatoma exhibited a significant correlation with the grade of otorrhea (R = 0.532, p = 0.039). Moreover, the period of epithelialization was also significantly associated with the relative expression levels of CYLD (R = 0.720, p = 0.002). In addition, CYLD expression tended to be lower in the group with recurrence. These results suggest that low CYLD expression correlates with postoperative recovery of acquired cholesteatoma, while potentially affecting the induction of recurrence. This is the first report showing that low CYLD expression correlates with accelerated disease recovery, and suggests a new aspect of CYLD as a prognostic predictor of acquired cholesteatoma.

Highlights

Middle ear cholesteatoma is a destructive disease characterized by abnormal growth of keratinized squamous epithelium [1,2]
In case we focused on the correlation with the presence or absence of recurrence, the relative expression level of CYLD in cholesteatoma tended to be lower in the group with recurrence, it was not significant (p = 0.115, Fig 3C)
We revealed the possibility that CYLD expression in acquired cholesteatoma correlates with clinicopathological characteristics, especially progression preoperatively and prognosis including infection, wound healing and recurrence in cholesteatoma patients

Summary

Introduction

Middle ear cholesteatoma is a destructive disease characterized by abnormal growth of keratinized squamous epithelium [1,2]. Clinical significance of CYLD in acquired cholesteatoma ventilation of the middle ear causes acquired cholesteatomatous otitis media [5]. There are various methods for classifying the degree of progression of acquired cholesteatoma, such as those proposed by Meyerhoff [7], Saleh & Mills [8], and Japan Otological Society (JOS) [9]. There is still no widely accepted classification for the acquired cholesteatoma in the world, and there are no biomarkers available for treatment selection and prognosis as used for other diseases. No clear correlation between the gene expression and prognosis has been obtained in acquired cholesteatoma. To improve the treatment of acquired cholesteatoma, clinically-useful biomarkers are urgently required

Methods

Results

Conclusion