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. 2025 May 22;17(11):1741.
doi: 10.3390/cancers17111741.

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

Karlijn van den Bovenkamp  1 , Gyorgy B Halmos  1 , Lorian Slagter-Menkema  1   2 , Boukje A C van Dijk  3   4 , Shibo Yu  2 , Johannes A Langendijk  5 , Bernard F A M van der Laan  1   6 , Ed Schuuring  2 , Bert van der Vegt  2
Affiliations

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

Karlijn van den Bovenkamp et al. Cancers (Basel). .

Abstract

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.

Keywords: DNA methyltransferase; immunohistochemistry; laryngeal squamous cell carcinoma; methylation; recurrence.

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Conflict of interest statement

B.v.d.V. reports scientific advisory board/consultancy (on request) for Visiopharm, Philips, MSD/Merck, and Daiichi-Sankyo/AstraZenica; speaker’s fees from Visiopharm, Diaceutics, and MSD/Merck; research grants from Philips, Owkin, and GE Healthcare (all to UMCG); and personal fees from DEKRA. All are unrelated to the present manuscript. ES reports lectures for Bio-Rad, Seracare, Novartis, Roche, Biocartis, Illumina, Lilly, Janssen Cilag, Pfizer, AstraZeneca, and Agena Bioscience; consultancy in advisory boards for MSD/Merck, GSK, AstraZeneca, Astellas Pharma, Roche, Pfizer, Novartis, Bayer, BMS, Lilly, Amgen, Biocartis, Illumina, Agena Bioscience, Janssen Cilag (Johnson&Johnson), Diaceutics, and CC Diagnostics; and received research grants from Pfizer, Biocartis, Invitae-ArcherDX, AstraZeneca, Agena Bio-science, BMS, Bio-Rad, Roche, Boehringer Ingelheim, CC Diagnostics, and Abbott (honoria paid to UMCG account).

Figures

Figure 1
Figure 1
Role of DNA methyltransferases in promoter hypermethylation and transcriptional silencing. Created in BioRender. van den Bovenkamp, K. (2025) https://BioRender.com/hhbl4f0 (accessed on 14 May 2025).
Figure 2
Figure 2
Immunohistochemical expression of DNMT1, DNMT3A, and DNMT3B (shown at 40× magnification).
See this image and copyright information in PMC

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