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.
Serum thyroglobulin (Tg) is the main biomarker for detecting persistent/recurrent thyroid cancer, although its specificity is limited in the presence of anti-Tg autoantibodies and residual normal thyroid tissue. The latter is being encountered with increasing frequency owing to the extensive use of a more conservative therapeutic approach. 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. Our previous study has been the first reporting the potential application of circulating miRNAs as biomarkers for monitoring PTC patients during long-term follow-up (up to 2 years after surgery treatment). We aim 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.
An important strength of the present study is the innovative technique we will use. Digital PCR (dPCR) is currently the only technique that can directly quantify the absolute number of nucleic acids. For this reason, dPCR should be the method of choice for validation studies and for setting diagnostic and prognostic tests. It also eliminates the need for standard curves and housekeeping genes required for qPCR, and it is also superior to the latter in terms of sensitivity, precision, and susceptibility to PCR inhibitors.