Background: Middle ear cholesteatoma is a locally destructive lesion that can cause severe complications and cannot be effectively managed with medical treatment alone. Although sirtuins are crucial epigenetic regulators of cellular metabolism, oxidative stress, and inflammatory responses, their specific roles in middle ear cholesteatoma remain unexplored. This study aimed to investigate the expression profiles of sirtuins and their association with the pathogenesis and clinical characteristics of cholesteatoma. Methods: The relative mRNA expression levels of seven sirtuin isoforms (SIRT1–7) were evaluated using quantitative real-time PCR in cholesteatoma tissues and matched postauricular skin controls obtained from 60 patients undergoing cholesteatoma surgery. Expression differences were analyzed according to tissue type, patient sex, and frequency of surgery (initial versus revision). Results: Clinically, otorrhea was observed in 58.3% of the patients, whereas the bacterial culture positivity rate was 16.7%. Conductive hearing loss was the predominant audiologic configuration. SIRT1–7 mRNA expression was detected in all cholesteatoma tissues, with SIRT1 exhibiting the highest relative expression, followed by SIRT4, SIRT3, SIRT6, SIRT7, SIRT5, and SIRT2. Notably, only the expression of SIRT7 was significantly downregulated in cholesteatoma tissues compared to postauricular skin controls (p = 0.002). No significant differences in SIRT1–7 expression were observed according to patient sex or history of revision surgery (p > 0.05). Conclusions: The distinct expression profiles of SIRT1–7 indicate their potential involvement in the pathogenesis of middle ear cholesteatoma. Although SIRT7 mRNA expression was lower in cholesteatoma tissue than in postauricular skin, this exploratory finding requires validation using tissue-appropriate controls and functional studies.
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