The Association Between Clinical Outcome and Expression of DNMT1, 3A, and 3B in Locally Advanced Laryngeal Carcinomas Treated by Definitive Radiotherapy

<b>Objectives</b>: This study aimed to evaluate the prognostic significance of DNA methyltransferases (DNMTs) expression, including DNMT1, DNMT3A, and DNMT3B, in assessing the risk of locoregional recurrence after radiotherapy in patients with locally advanced laryngeal squamous cell carcinoma (LSCC), in order to optimize treatment decision making. <b>Methods</b>: A retrospective analysis was performed on pre-treatment biopsy tissues and clinical data from 58 patients with locally advanced LSCC (stages T3-T4, M0) treated with primary curative radiotherapy. DNMT expression was assessed through immunohistochemistry, and Cox regression analysis was applied to examine associations between methylation marker expression, demographic and clinical data, and both locoregional recurrence and disease-specific mortality. <b>Results</b>: Low expression of DNMT3A (<i>p</i> = 0.045) and the presence of locoregional lymph node metastases at diagnosis (N+-status) (<i>p</i> = 0.002) were associated with disease-specific mortality. Clinical N-status was also associated with locoregional recurrent disease after primary radiotherapy (<i>p</i> < 0.001). Expression of DNMT1 and DNMT3B, age, sex, and clinical T-status were not associated with locoregional recurrences or disease-specific mortality. <b>Conclusions</b>: Low expression of DNMT3A and the presence of regional lymph node metastases were independently associated with disease-specific mortality in patients with locally advanced LSCC treated primarily with definitive, curatively intended radiotherapy.