Epigenetic Signature Enhances Prediction of Metastatic Thyroid Cancer Progression

Researchers from the Endocrine Tumors group at the Germans Trias i Pujol Research Institute (IGTP), in collaboration with five prominent university hospitals, have embarked on a comprehensive study to better understand metastatic differentiated thyroid cancer (DTC). Their focus was on analyzing DNA methylation patterns—an important epigenetic mechanism that influences gene expression—in various tumor stages. This groundbreaking research, published in the journal Thyroid, has identified a distinctive epigenetic signature consisting of 156 CpG sites in primary tumors. This signature can effectively stratify patients based on their likelihood of developing distant metastases.

DNA methylation plays a crucial role in the progression of thyroid cancer. The study involved analyzing samples from normal thyroid tissue, low-risk primary tumors, primary tumors from patients who later developed metastases, as well as lymph node and distant metastases. Findings revealed a progressive increase in methylation alterations corresponding with tumor advancement, primarily characterized by global hypomethylation. This supports a linear model of metastasis, where epigenetic changes accumulate over time.

Furthermore, the research highlighted differences in DNA methylation dynamics among the main histological subtypes of thyroid cancer, such as papillary (PTC) and follicular (FTC) carcinomas. While these subtypes display distinct methylation profiles during early stages, they tend to converge into similar epigenetic patterns during metastatic progression, indicating shared mechanisms in disease advancement regardless of initial tumor type.

A significant breakthrough from this study was the development of a prognostic tool based on the identified methylation signature. This panel of 156 CpG sites, validated in an independent patient cohort, allows for early prediction of patients at high risk of metastasis at the time of diagnosis. Such insights have the potential to improve personalized treatment plans and clinical management for thyroid cancer patients.

According to Mireia Jordà, principal investigator of the study, the findings underscore the critical role of DNA methylation changes in thyroid cancer progression. The success of this research was made possible through the multidisciplinary collaboration of multiple hospitals and the IGTP, emphasizing the importance of combined efforts in advancing precision medicine for rare and understudied tumors like thyroid cancer.

This research paves the way for new prognostic tools and reinforces the integration of epigenetic analysis into the clinical assessment of thyroid cancer, ultimately aiming to enhance patient outcomes through tailored therapies.

For more information, see the full study: Helena Rodríguez-Lloveras et al, DNA Methylation Dynamics and Prognostic Implications in Metastatic Differentiated Thyroid Cancer, Thyroid (2025). DOI: 10.1089/thy.2024.0303.

Source: https://medicalxpress.com/news/2025-04-epigenetic-signature-metastatic-thyroid-cancer.html