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

TL;DR

This study found that lower levels of DNMT3A and lymph node involvement are linked to higher mortality in laryngeal cancer patients treated with radiotherapy.

Contribution

The study identifies DNMT3A expression and lymph node status as novel prognostic markers for mortality in laryngeal cancer patients undergoing radiotherapy.

Findings

Low DNMT3A expression is associated with higher disease-specific mortality (p = 0.045).

Lymph node metastases at diagnosis are strongly linked to mortality (p = 0.002).

Clinical N-status is significantly associated with locoregional recurrence (p < 0.001).

Abstract

Locally advanced laryngeal cancer is challenging to treat, as it can return after primary treatments such as radiotherapy. This study examines the expression levels of certain proteins (DNMT1, DNMT3A, and DNMT3B) in tumor tissue, using immunohistochemistry to assess whether these protein levels are linked to the risk of cancer recurrence or mortality. By studying pre-treatment biopsy samples, we aimed to identify markers that could improve the estimation of treatment outcomes. Our results show that lower levels of the protein DNMT3A and the presence of lymph node involvement were associated with a higher risk of mortality. These findings may support more personalized treatment strategies and deepen the understanding of how these proteins relate to cancer progression.

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.

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