Association of MicroRNA Expression and BRAFV600E Mutation with Recurrence of Thyroid Cancer.

Daina Pamedytyte,Aurelija Zvirbliene,Valdas Sarauskas,Enrika Leipute,Rasa Verkauskiene,Albertas Dauksa,Vaida Simanaviciene,Dalia Dauksiene,Birute Zilaitiene

doi:10.3390/biom10040625

Daina Pamedytyte, Aurelija Zvirbliene + Show 7 more

Open Access

https://doi.org/10.3390/biom10040625

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Abstract

Many miRNAs and cancer-related mutations have been proposed as promising molecular markers of papillary thyroid carcinoma (PTC). However, there are limited data on the correlation between miRNA expression, BRAFV600E mutation, and PTC recurrence. Therefore, to evaluate the potential of BRAFV600E mutation and five selected miRNAs (-146b, -222, -21, -221, -181b) in predicting PTC recurrence, these molecular markers were analyzed in 400 formalin-fixed, paraffin-embedded PTC tissue specimens. The expression levels of miRNAs were measured using qRT-PCR. It was demonstrated that expression levels of all analyzed miRNAs are significantly higher in recurrent PTC than in non-recurrent PTC (p < 0.05). Moreover, higher expression levels of miR-146b, miR-222, miR-21, and miR-221 were associated with other clinicopathologic features of PTC, such as tumor size and lymph node metastases at initial surgery (p < 0.05). No significant differences in the frequency of BRAFV600E mutation in recurrent PTC and non-recurrent PTC were determined. Our results suggest that miRNA expression profile differs in PTC that is prone to recurrence when compared to PTC that does not reoccur after the initial surgery while BRAFV600E mutation frequency does not reflect the PTC recurrence status. However, the prognostic value of the analyzed miRNAs is rather limited in individual cases as the pattern of miRNA expression is highly overlapping between recurrent and non-recurrent PTC.

Highlights

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and it accounts for approximately 80% of thyroid cancer cases
We found that metastatic lymph nodes at the time of diagnosis and expression of miR-21 are associated with papillary thyroid carcinoma (PTC) recurrence and were independent prognostic factors of disease-free survival (DFS)
Summarizing, the analysis of five miRNA (-146b, -222, -221, -21, and -181b) expression levels in a large number of well-characterized PTC samples (n = 400) revealed that these miRNAs are overexpressed in PTC, but they are overexpressed in PTC with more aggressive features such as recurrence, bigger tumor size, lymph node metastasis, and shorter disease-free survival

Summary

Introduction

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and it accounts for approximately 80% of thyroid cancer cases. For most PTC patients the prognosis is good, and the 5-year survival rate is about 90% [1]. Up to 10% of PTC patients after primary tumor removal and treatment suffer regional or distant metastatic recurrence [2]. Fine-needle aspiration biopsy (FNAB) is the most widely used method for presurgical diagnosis of PTC malignancy. This method has many limitations and is not very sensitive—for up to 20% FNAB diagnosis is unclear and surgery is needed to evaluate malignancy [3]. The development of molecular markers of PTC recurrence such as miRNAs or BRAFV600E mutation has the potential to improve the clinical management of patients by assisting in risk stratification

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