Medullary thyroid carcinoma is a tumour whose diagnosis, to date, is based on the detection of high levels of calcitonin, a hormone produced by the thyroid C-cells from which the tumour originates, in patients with a thyroid nodule detected by ultrasound examination.

However, high calcitonin levels are not specific to such a neoplasm and can therefore also be found in patients without such a tumour. Moreover, the levels of this hormone, in the presence of neoplasia, do not always correlate with the extent of the tumour itself. Therefore, biomedical research is making great efforts to improve the diagnosis and consequently the prognosis of patients.

In this context, the research group coordinated by Elisabetta Ferretti and Agnese Po of Sapienza University of Rome used an innovative yet relatively inexpensive technology to identify new molecular features in the circulating DNA present in the blood of patients with medullary thyroid carcinoma. The study, a collaboration between three departments of Sapienza University of Rome and important national institutions such as the University of Siena, University of Pisa, University of Cagliari and the Pascale Institute in Naples, was published in the journal Biomarker Research of the Nature group.

"For some years now, the DNA circulating in the blood of cancer patients has been analysed for mutations in cancer cells. However, the number of different mutations that can be present is very high and investigations can miss the diagnosis because they look for the wrong molecule", says Agnese Po. “There are other characteristics of circulating DNA that can be exploited to identify a disease, and among these, we analysed methylation and fragmentation, which are linked to the phenotype and behaviour of cells".

By collecting liquid biopsy samples from patients with medullary thyroid carcinoma at the time of diagnosis to extract circulating DNA (or cell-free DNA), it is indeed possible to supplement the investigations that are already being performed, improving the level of patient characterisation.

"For these analyses, we used a highly specific technology such as digital PCR or droplet digital PCR”, says Elisabetta Ferretti, “which allows a resolution down to a single DNA molecule".

"These results", conclude Anna Citarella and Zein Mersini Besharat, first authors of the study and researchers at the Department of Experimental Medicine of Sapienza University, "lay the foundations for the addition of new non-invasive biomarkers, useful for the diagnosis and management of patients with medullary thyroid carcinoma in the context of precision medicine".

Moreover, these results open the way for the search for new circulating biomarkers also for other types of cancer, where the search for specific and sensitive diagnostic and prognostic biomarkers is an important medical need.

References:

Circulating cell-free DNA (cfDNA) in patients with medullary thyroid carcinoma is characterized by specific fragmentation and methylation changes with diagnostic value - Citarella A, Besharat ZM, Trocchianesi S, Autilio TM, Verrienti A, Catanzaro G, Splendiani E, Spinello Z, Cantara S, Zavattari P, Loi E, Romei C, Ciampi R, Pezzullo L, Castagna MG, Angeloni A, Elisei R, Durante C, Po A and Ferretti E - Biomarker Research (2023) https://doi.org/10.1186/s40364-023-00522-4

Further Information

Elisabetta Ferretti
Department of Molecular Medicine
elisabetta.ferretti@uniroma1.it

Agnese Po 
Department of Molecular Medicine
agnese.po@uniroma1.it