Role of DNA methylation-based mitotic ageing indices in oral cancer development and recurrence.

Autor: Ambatipudi S; Achutha Menon Centre for Health Science Studies, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Govt. Medical College Campus, Thiruvananthapuram, Kerala, India., Inchanalkar M; Mahimkar Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.; Homi Bhabha National Institute, Training School Complex, Mumbai, Maharashtra, India., Mahimkar MB; Mahimkar Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, Maharashtra, India.; Homi Bhabha National Institute, Training School Complex, Mumbai, Maharashtra, India.
Jazyk: angličtina
Zdroj: Oral diseases [Oral Dis] 2024 Jul; Vol. 30 (5), pp. 2929-2939. Date of Electronic Publication: 2023 Oct 16.
DOI: 10.1111/odi.14764
Abstrakt: Objective: DNA methylation data can be used to derive mitotic indices from complex tissues. Here, we assessed if the DNA methylation-derived mitotic ageing indices are associated with oral squamous cell carcinoma (OSCC) development and recurrence-free survival (RFS).
Methods: DNA methylation-based mitotic indices (MitoticAge, TNSC and hypoSC) were derived using algorithms "MitoticAge" and "epiTOC2" for the discovery [non-malignant (n = 22), premalignant (n = 22) and OSCC (n = 68) tissues] and validation datasets (GSE87053, GSE136704 and TCGA-HNSCC). Differences in mitotic indices between non-malignant, premalignant and OSCC tissues were assessed. Finally, the association between estimated mitotic indices and RFS was evaluated in OSCCs.
Results: In the discovery and validation datasets, increased mitotic ageing was observed in OSCC compared to non-malignant and premalignant oral tissues. HPV-positive HNSCCs had higher mitotic index TNSC. Mitotic age index hypoSC was associated with RFS in OSCC (p = 0.011, HR 2.61, 95% CI 1.24-5.48).
Conclusions: DNA methylation-derived mitotic indices are associated with OSCC development and RFS. Thus, DNA methylation-derived mitotic indices may be a valuable research tool to reliably estimate the cumulative number of stem cell divisions in malignant and non-malignant oral tissues. Future research utilizing mitotic indices for predicting clinical outcomes in OSCC is warranted.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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