Identification of exosomal miRNA biomarkers for diagnosis of papillary thyroid cancer by small RNA sequencing.

Abstract

Exosomal miRNAs are considered potential non-invasive biomarkers for thyroid cancer. However, the global exosomal miRNAs profile for papillary thyroid cancer (PTC) has not been revealed. This study investigated the diagnostic value of plasma and serum exosomal miRNAs for PTC. Plasma and serum samples were collected from ten patients with benign thyroid nodules and 17 with PTC for small RNA sequencing. Plasma samples were collected from two independent cohorts, including 119 patients with PTC, 51 healthy people and 82 patients with benign thyroid nodules, for validation by quantitative reverse-transcription polymerase chain reaction (RT-qPCR). Small RNA sequencing identified 41 putative exosomal miRNA biomarkers for PTC. Twelve miRNAs were selected for validation. miR-376a-3p, miR-4306, miR-4433a-5p, and miR-485-3p expression significantly increased in patients with PTC compared to that in healthy people and patients with benign thyroid nodules (P ˂ 0.05). Moreover, miR-485-3p and miR-4433a-5p presented larger areas under the curve (AUCs). The high expression of exosomal miR-485-3p correlated with tumor size greater than or equal to 1 cm, advanced clinical stage, extrathyroidal extension, BRAF mutation, and lymph node metastasis. Besides, miR-485-3p exhibited the highest AUCs in diagnosing PTC patients with high-risk factors. Plasma exosomal miR-485-3p and miR-4433a-5p might serve as biomarkers for PTC diagnosis. Plasma exosomal miR-485-3p could enable discrimination between high-risk and low-risk PTC.