Potential use of circulating microRNAs in thyroid cancer follow-up
For the growing population of patients with papillary thyroid carcinoma (PTC), the 2015 American Thyroid Association guidelines recommend less extensive surgery, more selective use of radioiodine remnant ablation, and, in some cases, even active surveillance alone. One "side effect" of this change is a diagnostic gap in posttreatment surveillance protocols. The reliability of serum Tg assay results declines substantially in patients with residual normal thyroid tissue. Consequently, clinicians are increasingly faced with a need for more accurate biomarkers to monitor these patients for persistent/recurrent disease.
Research on circulating microRNAs (miRNAs) is providing new insights for the development of novel biomarkers that can be used to optimize posttreatment follow-up of PTC patients.
We previously identified two circulating miRNAs (miR-146a-5p and miR-221-3p) which showed remarkable promise as serum biomarkers for posttreatment monitoring of PTC patients. In the patients with excellent/indeterminate responses or biochemical incomplete responses, circulating levels of both miRNAs progressively declined after surgery. In contrast, in the patients with structural incomplete responses, serum miRNA levels increased between the 30-day and 1- to 2-year observation points, including two cases with lymph node metastases and serum Tg consistently negative. Thus, miR-146a-5p and miR-221-3p accurately predicted the disease status of all patients and both were better for detecting lymph node metastases than serum Tg assays.
Aim of the present study is to validate our previous findings in a larger cohort including also patients with aggressive PTC, which underwent treatment with radioactive iodine and/or tyrosine kinase inhibitor. Furthermore, we will use digital PCR, an innovative, sensitive and precise technique which enables the direct and absolute quantification of miRNAs, thus eliminating the need for standard curves and housekeeping genes required for qPCR.