Objectives: 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.Methods: 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.Results: Low expression of DNMT3A (p= 0.045) and the presence of locoregional lymph node metastases at diagnosis (N+-status) (p= 0.002) were associated with disease-specific mortality. Clinical N-status was also associated with locoregional recurrent disease after primary radiotherapy (p< 0.001). Expression of DNMT1 and DNMT3B, age, sex, and clinical T-status were not associated with locoregional recurrences or disease-specific mortality.Conclusions: 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.
目的:本研究旨在评估DNA甲基转移酶(DNMTs,包括DNMT1、DNMT3A和DNMT3B)的表达对局部晚期喉鳞状细胞癌(LSCC)患者放疗后局部区域复发风险的预后意义,以优化治疗决策。 方法:对58例接受根治性放疗的局部晚期LSCC患者(T3–T4期,M0)的治疗前活检组织和临床资料进行回顾性分析。通过免疫组织化学方法评估DNMT表达,并应用Cox回归分析检验甲基化标志物表达、人口统计学和临床数据与局部区域复发及疾病特异性死亡率之间的关联。 结果:DNMT3A的低表达(p=0.045)和诊断时存在局部区域淋巴结转移(N+状态)(p=0.002)与疾病特异性死亡率相关。临床N状态也与初次放疗后的局部区域复发疾病相关(p<0.001)。DNMT1和DNMT3B的表达、年龄、性别和临床T状态与局部区域复发或疾病特异性死亡率无关。 结论:在接受根治性放疗的局部晚期LSCC患者中,DNMT3A的低表达和区域淋巴结转移的存在与疾病特异性死亡率独立相关。