MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer

Abstract

Despite low mortality rates, nodal recurrence in papillary thyroid carcinoma occurs in up to 20 % of patients. Emerging evidences indicate that dysregulated microRNAs are implicated in the process of metastasis. In the present study, we investigated whether miR-9, miR-10b, miR-21 and miR-146b levels are predictive of papillary thyroid carcinoma recurrence. Using macro-dissection followed by quantitative real-time PCR, we measured miR-9, miR-10b, miR-21 and miR-146b expression levels in formalin-fixed, paraffin-embedded samples of 66 patients with papillary thyroid carcinoma categorized into two groups: the recurrent group (n = 19) and the non-recurrent group (n = 47). All patients underwent total thyroidectomy and were followed for at least 120 months after surgery to be considered recurrence-free. Univariate and multivariate analysis were performed using the Cox proportional hazard model in order to identify associations between multiple clinical variables and microRNA expression levels and papillary thyroid carcinoma recurrence. MiR-9 and miR-21 expression levels were found to be significant prognostic factors for recurrence in patients with papillary thyroid carcinoma (HR = 1.48; 95 % CI 1.24-1.77, p < 0.001; and HR = 1.52; 95 % CI 1.18-1.94, p = 0.001; respectively). Multivariate analysis involving the expression level of miR-9 and miR-21 and various clinical parameters identified the expression of these microRNAs as independent prognostic factors for papillary thyroid cancer patients. In conclusion, our results support the potential clinical value of miR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid carcinoma.

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

“…In TCGA data, a more aggressive phenotype of thyroid cancer was also correlated with overexpression of miR-21 and miR-146b, as well as the loss of miR-204 (47). Later, the expression levels of miR-21 and miR-9 were also associated with the metastatic potential of tumor cells and proved to be good predictors of nodal metastasis (53).…”

Pathobiology of MicroRNAs and Their Emerging Role in Thyroid Fine-Needle Aspiration

“…However, only sporadic studies have so far focused on the association between miR deregulation and thyroid cancer prognosis and therapy [40,55,56,57,58,59]. …”

“…Therapeutic inhibition of miR-146b in dedifferentiated thyroid carcinoma represents a promising way to enhance radioiodine uptake and the efficacy of radioactive therapy [57]. However, Sondermann et al [59] found no significant differences in miR-146b expression between recurrent and nonrecurrent papillary carcinomas.…”

MicroRNA‑335 is downregulated in papillary thyroid cancer and suppresses cancer cell growth, migration and invasion by directly targeting ZEB2

“…Thyroid cancer is the most common subtype of endocrine malignancy, with 300,000 new cases per year, and ~40,000 mortalities per year, worldwide (1). The incidence of thyroid cancer has increased in recent decades (2).…”