Absolute quantification of circulating miR-146a-5p and miR-221-3p in the detection of pre-operative papillary thyroid cancers

  • BACKGROUND Liquid biopsy represents a source of tumor-derived material alternative to tissue biopsy and could be useful in preoperative diagnosis and/or in the post-operative follow-up of oncologic patients. Our group previously identified miR-146a-5p and miR-221-3p as the two most accurate circulating miRNAs in discriminating between PTCs and healthy control (HC)1. In the present study, we have further tested their discriminating ability in a new different cohort of sera of patients with PTC before undergoing thyroidectomy (preoperative PTCs) and HCs using a highly sensitive methodology for their absolute quantification. METHODS Using digital-PCR we analyzed miR-146a-5p and miR-221-3p levels in serum samples of 73 pre-operative PTCs and 45 age- and sex-matched healthy controls. We used cel-miR-39 as the spiked-in control. RESULTS For miR-146a-5p we obtained a mean value of 2.42×105±1.24×105and 1.45×105±1.03×105 (P<0.0001) and for miR221 a mean value of 1.77×105±1.32×105and 5.97×104±5.66×104 (P<0.0001) respectively in PTCs versus HCs. Data are expressed as absolute copy number for ul of serum. The ROC curve analysis reported an AUC of 0.78 for miR-146a-5p and 0.86 for miR-221-3p. We selected a cut-off of 160,000 for miR-146a-5p (77% sensitivity and 71%specificity) and of 82,450 for miR-221-3p (81% sensitivity and 82% specificity). DISCUSSION AND CONCLUSIONS The present findings demonstrate that circulating miR-146a-5p and miR-221-3p have a good ability in discriminating PTCs versus HCs. The ability of both miRNAs to identify the presence of thyroid cancer could potentially be helpful in the clinical practice for PTC patient’s management, as markers of disease status during patient’s follow-up.


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