Serum microRNA-146a-5p and microRNA-221-3p as potential clinical biomarkers for papillary thyroid carcinoma

Abstract

Purpose: Papillary thyroid carcinoma (PTC) is the most common malignant thyroid neoplasm, accounting for approximately 85% of all follicular cell-derived thyroid nodules. This study aimed to assess the diagnostic potential of circulating microRNA-146a-5p and microRNA-221-3p as biomarkers for PTC and their usefulness in monitoring disease progression during patient follow-up.

Methods: An observational study was conducted on two cohorts of PTC patients and healthy controls (HCs) using digital PCR. We collected patients' clinical, biochemical, and imaging data during the post-surgery surveillance. We analyzed the levels of circulating miRNAs in serum samples of patients before surgery and during the follow-up, including those with indeterminate/biochemical incomplete response (IndR/BIR) and residual thyroid tissues (Thy Residue).

Results: Both miR-146a-5p and miR-221-3p were confirmed as effective biomarkers for PTC diagnosis. They enabled differentiation between pre-surgery PTC patients and HCs with an area under the curve (AUC) of 92% and 87.3%, respectively, using a threshold level of 768,545 copies/uL for miR-146a-5p and 389,331 copies/uL for miR-221-3p. It was found that miRNA fold change levels, rather than absolute levels, can be useful during patient follow-up. In particular, we found that a fold change of 2 for miR-146a-5p and 2.2 for miR-221-3p can identify a progressive disease, regardless of the presence of TgAbs or remnant thyroid.

Conclusion: MiRNA-146a-5p and miRNA-221-3p, particularly the former, could be valuable diagnostic biomarkers for PTCs. They also seem to be effective in monitoring disease progression during patient follow-up by evaluating their fold change, even when thyroglobulin is uninformative.

Keywords: Biomarkers; Circulating miRNA; Liquid biopsy; Papillary thyroid cancer; Patient follow-up.

Fig. 1

ROC analysis of miRNA levels in the sera of pre-surgery PTC and healthy subjects

Fig. 2

miR levels in the first (ER I) and second (ER II) post-operative serum samples from patients with excellent response (ER). The lines represent the cut-off calculated between pre-surgery PTC and HC sera

Fig. 3

miRNA levels in the first (SIR I) and second (SIR II) post-operative serum samples from patients with structural incomplete response and either progressive (pSIR) or stable (sSIR) disease. The lines represent the cut-off calculated between pre-surgery PTC and HC sera

Fig. 4

miRNA fold change values between the two post-surgery blood samples from patients with excellent response (ER) and patients with structural incomplete response and progressive (pSIR) or stable (sSIR) disease

Fig. 5

ROC analysis conducted on the miRNA fold changes between the two post-surgery blood samples to distinguish patients with excellent response to surgery (ER) and structural incomplete response with stable disease (sSIR) from those with structural incomplete response and progressive (pSIR) disease

Fig. 6

Panel a: miR levels in the first (IndR/BIR I) and second (IndR/BIR II) post-operative serum samples from patients with an indeterminate and biochemical incomplete response. Panel b: miR levels in the first (Thy Residue I) and second (Thy Residue II) post-operative serum samples from patients with residual thyroid tissue. The lines represent the cut-off calculated between pre-surgery PTC and HC sera

Fig. 7

miRNA fold change values between the two post-surgery blood samples from patients with indeterminate and biochemical incomplete response (IndR/BIR) and residual thyroid tissue (Thy Residue). The lines represent the cut-off to distinguish patients with excellent response to surgery (ER) and structural incomplete response with stable disease (sSIR) from those with structural incomplete response and progressive (pSIR) disease