From Circulating Tumor Cells to Mirna: New Challenges in the Diagnosis and Prognosis of Medullary Thyroid Cancer

Abstract

Medullary thyroid carcinoma (MTC) is a malignant tumor that arises from parafollicular C cells, which are responsible for producing calcitonin. The majority (75%) of MTC cases are sporadic forms, while the remaining (25%) have a hereditary component. In these hereditary cases, MTC can occur in conjunction with other endocrine disorders (i.e., pheochromocytoma) or as an isolated condition known as familial medullary thyroid carcinoma. The primary genetic mutation associated with the development of MTC, regardless of its hereditary or sporadic nature, is a point mutation in the RET gene. Evaluation of serum calcitonin levels represents the most reliable and sensitive marker for both the initial diagnosis and the postsurgical monitoring of MTC. Unfortunately, most patients do not achieve normalization of postsurgical serum calcitonin (CT) levels after surgery. Therefore, there is a need to find new biomarkers to be used with serum CT in order to increase test sensitivity and specificity. In this review, we summarize the literature from 2010 to 2023 to review the role of circulating tumor cells, cell-free DNA, and miRNA and their application in diagnosis, outcome of MTC, and response to treatments.

The Circulating Biomarkers League: Combining miRNAs with Cell-Free DNAs and Proteins

“…Current research efforts are directed towards enhancing the accuracy and reliability of cfDNA-based assays to bolster their applicability in diagnosing and managing different forms of cancer. Nevertheless, the bulk of research predominantly concentrates on analyzing the mutation patterns within cfDNA [ 160 ].…”

Advances in targeted therapy and biomarker research in thyroid cancer

“…Furthermore, studies have shown intriguing biomarkers that indicate therapy response, which might help with treatment selection. By evaluating circulating tumor DNA, liquid biopsies provide a non-invasive way to track the course of the illness and identify recurrences before they become severe ( 39 ). Clinical practice may greatly benefit from the integration of molecular profiling in order to improve patient outcomes, risk classification, and customized treatment plans.…”

MicroRNAs in thyroid cancer with focus on medullary thyroid carcinoma: potential therapeutic targets and diagnostic/prognostic markers and web based tools

“…Nevertheless, in certain cases, calcitonin levels may not normalize after surgery, resulting in an imprecise diagnosis and suboptimal patient care. New biomarkers are required to be found that can complement serum calcitonin and boost the accuracy and precision of the diagnosis [ 37 ].…”

“…The miR-375, miR-17-5p, and miR-222-3p have demonstrated high discriminating accuracy and could be potential biomarkers for MTC. Hence, certain miRNAs, such as miR-375, have shown significant promise in diagnosis and prognosis and could be of great interest to future studies on treatment response [ 37 ].…”