Identification of a Novel, Diagnostic microRNA Signature in Papillary Thyroid Cancer

Abstract

Diagnosis is based on ultrasound and fine needle aspiration pathological findings. Screening asymptomatic people as well as those being at normal risk for thyroid cancer is not recommended. "Molecular signatures" consisting of miRNAs could be accounted for as promising diagnostic and/or prognostic biomarkers for different human malignancies, including thyroid cancer. MicroRNA molecules, being stable in blood and urine, are ideal components of molecular signatures. In this study, we sought to identify a molecular signature that could be used to diagnose papillary thyroid cancer with high sensitivity and specificity. For this purpose, we performed miRNA-seq to identify and quantify miRNAs showing high difference in their expression levels in serum of patients with papillary thyroid cancer and other diseases of thyroid and/or normal population. Validation was performed using real-time PCR. Using this approach, we found eight miRNAs being significantly over-or underexpressed in papillary thyroid cancer tissues compared to their normal counterparts (normal thyroid tissues): miR-144-3p, miR-622, miR-361-5p, miR-146a-3p, miR-340-5p, miR-199a-5p, miR-335-5p, and miR-129-5p. Five out of these eight miRNAs are also significantly over-or under-represented in blood serum of patients with papillary thyroid cancer. In conclusion, our study shows, for the first time, that a molecular signature consisting of miR-144-3p, miR-146a-3p, miR-340-5p, miR-199a-5p and miR-335-5p, is able to diagnose with high sensitivity and specificity papillary thyroid cancer in patients' blood serum.

Comprehensive transcriptomic analysis of Papillary Thyroid Cancer: potential biomarkers associated with tumor progression

“…However the deregulation of several identified miRNAs in this study has previously been well confirmed in PTC (bold fonts in Table 5). Among previously reported deregulated miRNAs, the upregulation of hsa-miR-146b and hsa-miR-222 and the down-regulation of hsa-miR-144 have been also reported in the blood of PTC patients (Poulios et al, 2018, Yu et al, 2012. A similar comparison to that of mRNAs was also carried out for differential expressed miRNAs to identify further deregulation of their expression in higher stages.…”

Comprehensive transcriptomic analysis of papillary thyroid cancer: potential biomarkers associated with tumor progression

“…However the deregulation of several identified miRNAs in this study has previously been well confirmed in PTC (bold fonts in Table 5). Among previously reported deregulated miRNAs, the upregulation of hsa-miR-146b and hsa-miR-222 and the down-regulation of hsa-miR-144 have been also reported in the blood of PTC patients [21,22]. A similar comparison to that of mRNAs was also carried out for differential expressed miRNAs to identify further deregulation of their expression in higher stages.…”