BRIEF RESEARCH REPORT article

Front. Oral Health

Sec. Oral Cancers

Volume 6 - 2025 | doi: 10.3389/froh.2025.1614371

Salivary cell-free DNA methylation analysis for oncological monitoring of surgical resection of Oral Squamous Cell Carcinoma

Provisionally accepted
  • Centre Hospitalier Universitaire (CHU) d'Amiens, Amiens, France

The final, formatted version of the article will be published soon.

Objective: Non-invasive analysis of tumor DNA in biological fluids offers promising perspectives for the oncological monitoring of cancer patients. Cancer-specific DNA methylation marks are detectable in the saliva of Oral Squamous Cell Carcinoma (OSCC) patients. We set up a salivary liquid biopsy approach for the oncological monitoring of OSCC referred for surgical resection. Material and methods: We analysed DNA methylation in TCGA-OSCC to identify genes with high methylation levels in tumor vs matched non-tumor tissue. Cell-free DNA (cfDNA) methylation levels of selected genes were analysed in the saliva of OSCC patients (n=30) before / after complete surgical resection by High Resolution Melting (HRM) analysis, and compared to non-cancer controls. Results: We identified five genes with higher DNA methylation levels in OSCC compared to matching non-tumor tissue that were analysable by HRM, and were independent of tumor stage, etiology or age. In 70% of OSCC, at least one of the five cfDNA methylation marks was detectable before surgery. Complete surgical resection led to a significant disappearance of salivary cfDNA methylation marks. In 52% of patients, we noted the persistence of at least one mark, shown to be related to close/positive surgical margin status. In one patient resected with R0 margin, the persistence of ASCL1 methylation preceded tumor recurrence by 4 months. Conclusion: Salivary cfDNA methylation analysis offers a minimally invasive method to monitor the effectiveness of surgical resection of OSCC. Future studies with a larger cohort and longer follow-up are required to validate its use in this context.

Keywords: oral squamous cell carcinoma, surgical resection, Saliva, cell-free DNA methylation, biomarkers

Received: 18 Apr 2025; Accepted: 27 May 2025.

Copyright: © 2025 Saidak, Milly, Louandre, Colin, Rusu, Paasche, Dakpé, Testelin and Galmiche. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Zuzana Saidak, Centre Hospitalier Universitaire (CHU) d'Amiens, Amiens, France

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