MicroRNA Profile for Diagnostic and Prognostic Biomarkers in Thyroid Cancer

SIMPLE SUMMARY: Thyroid nodules are frequently detected, but the majority of these nodules are benign. Molecular markers have become useful for diagnosing the minority of thyroid cancer. We performed high-throughput small RNA sequencing in a discovery cohort and identified three miRNAs (miR-136, miR-21, and miR-127) as potential biomarkers for thyroid cancer. We validated the diagnostic and prognostic utilities of three miRNAs in patients with thyroid cancer in an independent cohort. High expression of the three miRNAs could be used to differentiate thyroid cancers from benign tumors and tumors with extremely low malignant potential. In patients with thyroid cancers, a high expression of three miRNAs was associated with poor clinicopathological features and recurrent or persistent disease following surgery. Therefore, testing for high expression levels of these three miRNAs in thyroid nodules may be useful for diagnosing and assessing the recurrence of the thyroid cancer’s risk stratification. ABSTRACT: The challenge in managing thyroid nodules is to accurately diagnose the minority of those with malignancy. We aimed to identify diagnostic and prognostic miRNA markers for thyroid nodules. In a discovery cohort, we identified 20 candidate miRNAs to differentiate between noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP) and papillary thyroid carcinomas (PTC) by using the high-throughput small RNA sequencing method. We then selected three miRNAs (miR-136, miR-21, and miR-127) that were differentially expressed between the PTC follicular variant and other variants in The Cancer Genome Atlas data. High expression of three miRNAs differentiated thyroid cancer from nonmalignant tumors, with an area under curve (AUC) of 0.76–0.81 in an independent cohort. In patients with differentiated thyroid cancer, the high-level expression of the three miRNAs was an independent indicator for both distant metastases and recurrent or persistent disease. In patients with PTC, a high expression of miRNAs was associated with an aggressive histologic variant, extrathyroidal extension, distant metastasis, or recurrent or persistent disease. Three miRNAs may be used as diagnostic markers for differentiating thyroid cancers from benign tumors and tumors with extremely low malignant potential (NIFTP), as well as prognostic markers for predicting the risk of recurrent/persistent disease for differentiated thyroid cancer.