MicroRNA expression signatures associated with metastatic progression in papillary thyroid carcinoma.

OBJECTIVE: The objective of this study is to compare the miRNA expression profiles of primary tumors and matched metastatic lesions from patients who died due to progression of metastatic PTC. SUBJECTS AND METHODS: We conducted an exploratory study of patients with PTC who died from disease progression and had tissue samples available from both primary tumors and distant metastases. Total RNA was extracted and analyzed to assess the expression of 64 preselected miRNAs. Expression data were normalized using endogenous controls (let-7g-5p and miR-181a-5p), and differential expression was calculated using the 2-∆Ct method. Those miRNAs detected in < 70% of samples or with cycle threshold (Ct) > 36 were excluded. Univariate analyses were performed using paired tests, and multivariate results were adjusted for multiple comparisons using the Benjamini-Hochberg false discovery rate (FDR) method. RESULTS: Out of 3,555 patients treated for PTC between 1986 and 2015, eight patients were included. Univariate analysis identified five miRNAs differentially expressed in metastatic lesions: let-7e-5p, miR-10b-5p, miR-30e-3p, miR-423-5p, and miR-483-3p. After multivariate adjustment, miR-10b-5p and miR-30e-3p remained independently overexpressed in metastatic tissues. CONCLUSION: This study is one of the first to demonstrate distinct miRNA expression profiles in metastatic versus primary tumors in fatal PTC cases. The identified miRNAs are known to regulate processes such as cell migration, invasion, and apoptosis in other cancers, suggesting their potential contribution to PTC metastasis.