A groundbreaking study led by the Endocrine Tumours Group at the Germans Trias i Pujol Research Institute (IGTP), in collaboration with five university hospitals, has revealed new insights into the progression of differentiated thyroid cancer (DTC) through the lens of DNA methylation, a central epigenetic mechanism that regulates gene expression. Published in the prestigious journal Thyroid, the study is the first of its kind to offer a comprehensive analysis of DNA methylation patterns associated with metastatic thyroid cancer and introduces a promising biomarker that could transform the clinical management of the disease.

The researchers conducted an in-depth analysis of DNA methylation profiles in a wide spectrum of thyroid tissue samples—including normal thyroid, low-risk primary tumors, primary tumors from patients who developed distant metastases, and samples of both lymph node and distant metastases. The data revealed a clear trend: as thyroid cancer progresses, DNA methylation patterns undergo increasingly widespread changes, predominantly marked by global hypomethylation. This progressive shift supports a linear model of metastasis, suggesting that early epigenetic alterations may be predictive of more aggressive disease trajectories.

One of the most striking findings of the study is the identification of a specific DNA methylation signature comprising 156 CpG sites in primary tumors. This epigenetic signature was consistently found in patients who later developed distant metastases and was further validated in an independent patient cohort. This discovery could provide clinicians with a critical prognostic tool, enabling the early identification of high-risk patients at diagnosis and guiding more targeted, personalized treatment strategies.

The research also sheds light on the biological differences between the two main histological subtypes of thyroid cancer: papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC). While each subtype exhibits distinct DNA methylation profiles in early disease stages, the study found that these patterns tend to converge during metastatic progression. This convergence suggests the involvement of shared epigenetic mechanisms that could be exploited therapeutically, regardless of the tumor’s origin.

This study confirms that changes in DNA methylation play a key role in the progression of thyroid cancer and bring us closer to the early identification of high-risk patients,said Dr. Mireia Jordà, principal investigator of the study and head of the Endocrine Tumours Group at IGTP. The collaboration between multiple hospitals and research institutions has been essential in ensuring the strength and reliability of our findings. It also highlights the importance of interdisciplinary efforts in advancing precision medicine, especially for cancers like thyroid, which have historically received less attention.

This landmark study not only enhances our understanding of thyroid cancer biology but also reinforces the growing importance of integrating epigenetic data into cancer diagnosis and treatment. By identifying and validating a robust methylation-based biomarker, the research team has laid a solid foundation for future clinical tools that can improve prognostic accuracy and individualize care for patients with thyroid cancer.

As the field of oncology continues to evolve, studies like this one illustrate the transformative potential of epigenetics in developing safer, more effective, and highly tailored treatment strategies.

Source: https://biotech-spain.com/en/articles/igtp-led-study-identifies-an-epigenetic-signature-with-prognostic-value-in-metastatic-thyroid-cancer/