Association of microRNA Expression and BRAFV600E Mutation with Recurrence of Thyroid Cancer

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.

Plasma-Derived miRNA-222 as a Candidate Marker for Papillary Thyroid Cancer

“…Previous studies have demonstrated that miR-146b, miR-221 and miR-222 are the most consistently overexpressed miRNAs in PTC tissue [ 14 , 22 , 45 , 46 ]. Moreover, studies that explored miR-146b, miR-222 and miR-221 expression in plasma samples showed their consistent upregulation in PTC compared to the HC group [ 22 , 40 ].…”

“…It is already known that miR-146b, miR-21, miR-221, miR-222, miR-181b are dysregulated in PTC. These molecules showed potential as biomarkers in PTC tissue and plasma/serum studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. It was also demonstrated that downregulation of miR-181b inhibits proliferation and promotes apoptosis in thyroid cancer TPC1 cells, making this miRNA a possible target for PTC treatment [ 24 ].…”

The Impact of BRAF Mutation on the Recurrence of Papillary Thyroid Carcinoma: A Meta-Analysis

“…Our results using HR confirmed that the BRAF V600E mutation is not associated with recurrence. Recent studies have indicated that the effect of the BRAF V600E mutation for PTC recurrence would be minimized, or even be protective, after adjustment of possible confounders including age, sex, tumor size, and multifocality [21,26,28]. Pamedytete et al reported that the adjusted HR of the BRAF V600E mutation was 0.80 (95% CI 0.47-1.36), although the unadjusted HR was 1.01 (95% CI 0.62-1.64) for the recurrence of PTC [21].…”

“…Recent studies have indicated that the effect of the BRAF V600E mutation for PTC recurrence would be minimized, or even be protective, after adjustment of possible confounders including age, sex, tumor size, and multifocality [21,26,28]. Pamedytete et al reported that the adjusted HR of the BRAF V600E mutation was 0.80 (95% CI 0.47-1.36), although the unadjusted HR was 1.01 (95% CI 0.62-1.64) for the recurrence of PTC [21]. In the present meta-analysis, the pooled HR of the enrolled studies also decreased from 1.30 (95% CI 0.91-1.85) to 1.16 (95% CI 0.78-1.71) after adjustment, which is consistent with the previous reports.…”

“…Only Wang et al used HRs to investigate the role of the BRAF V600E mutation in the recurrence rates of PTC, but this study had some limitations, such as the inclusion of duplicate studies and inaccurate estimation of HRs in some enrolled studies [20]. Furthermore, several studies using large cohorts have been reported recently after the publication of that meta-analysis [21][22][23][24][25][26][27][28].…”