Researchers from the Endocrine Tumours group at the Germans Trias i Pujol Research Institute (IGTP), in collaboration with five university hospitals, have conducted the first comprehensive study of DNA methylation patterns in metastatic differentiated thyroid cancer (DTC). Published in the journal Thyroid, the study identifies an epigenetic signature comprising 156 CpG sites in primary tumours that could help stratify patients according to their risk of developing distant metastases.
The study provides new insights into the role of DNA methylation-a key epigenetic mechanism in gene expression regulation-in thyroid cancer progression. These findings contribute to a better understanding of the disease and open new avenues for patient stratification and personalised treatment strategies.
A multicentre analysis of DNA methylation
The researchers analysed samples from normal thyroid tissue, low-risk primary tumours, primary tumours from patients who later developed metastases, lymph node metastases, and distant metastases. The results show a progressive increase in DNA methylation alterations during tumour progression, predominantly characterised by global hypomethylation, supporting a linear model of metastasis.
The study also highlights differences in DNA methylation dynamics between the main histological subtypes of thyroid cancer. While papillary (PTC) and follicular (FTC) carcinomas exhibit distinct methylation profiles in the early stages, both converge towards common epigenetic patterns during metastatic progression. These findings suggest shared epigenetic mechanisms in advanced stages of the disease, regardless of the initial tumour subtype.
A tool for metastasis prediction
The detailed analysis enabled the identification of a specific signature of 156 altered CpG sites in primary tumours from patients with distant metastases, validated in an independent cohort. This signature represents a promising prognostic tool for the early identification of high-risk patients at diagnosis, improving risk stratification and supporting the adoption of personalised clinical management strategies for thyroid cancer.
"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. The collaboration between five university hospitals and the IGTP has been essential to ensure the robustness of the results and highlights the importance of multidisciplinary research in advancing precision medicine for less-studied tumours such as thyroid cancer," says Mireia Jordà, principal investigator of the study and leader of the Endocrine Tumours Group at IGTP.
This research lays the groundwork for improving prognostic tools in thyroid cancer and reinforces the value of incorporating epigenetic analysis into personalised care strategies for patients with this disease.
