Role of tissue and circulating microRNAs and DNA as biomarkers in medullary thyroid cancer.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor comprising hereditary or sporadic form with frequent mutations in the rearranged during transfection (RET) or RAS genes. Diagnosis is based on the presence of thyroid tumor mass with altered levels of calcitonin (Ctn) and carcinoembryonal antigen (CEA) in the serum and/or in the cytological smears from fine needle aspiration biopsies. Treatment consists of total thyroidectomy, followed by tyrosine kinase inhibitors (TKi) in case of disease persistence. During TKi treatment, Ctn and CEA levels can fluctuate regardless of tumor volume, metastasis or response to therapy. Research for more reliable non-invasive biomarkers in MTC is still underway. In this context, circulating nucleic acids, namely circulating microRNAs (miRNAs) and cell free DNA (cfDNA), have been evaluated by different research groups. Aiming to shed light on whether miRNAs and cfDNA are suitable as MTC biomarkers we searched three different databases, PubMed, Scopus, WOS and reviewed the literature. We classified 83 publications fulfilling our search criteria and summarized the results. We report data on miRNAs and cfDNA that can be evaluated for validation in independent studies and clinical application.