Kosin Med J.  2020 Jun;35(1):1-14. 10.7180/kmj.2020.35.1.1.

Expressions of miRNAs in Papillary Thyroid Carcinoma and Their Associations with the BRAF^V600EMutation and Clinicopathological Features.

• Yang SI
• Choi YS

• KMID: 2503724
• DOI: http://doi.org/10.7180/kmj.2020.35.1.1

Abstract

Objectives
The microRNAs (miRNAs) are known to be commonly expressed in papillary thyroid carcinoma. The BRAF^V600Emutation is the most common genetic mutation in thyroid cancer. The main aim of this study was to determine the possible association between expression of the three miRNAs and that of BRAF^V600E mutation and the clinicopathological features in papillary thyroid carcinoma.
Methods
This study was conducted on 51 paraffin-embedded tissues (42 thyroid cancer, 9 benign tumor) obtained from patients undergoing thyroidectomy at the Endocrine Center of OOO University Hospital.
Results
miRNAs expression was significantly high in patients with cervical lymph node metastasis and advanced TNM stage. In addition, miR-146b expression levels were significantly higher in papillary thyroid carcinoma patients with BRAF^V600E mutation. The relative quantification (2-^△△Ct) of miR-146b was also high among the miRNAs. Individually, the AUCs for miRNA-146b was 0.923 (cutoff value -1.97, sensitivity 88.9%, specificity 85.7%).
Conclusions
Especially, expression of miR-146b increased higher in PTC patients with BRAF^V600Emutation. These findings showed a role of miR-146b as potential biomarkers in differentiating PTC from benign tumor and as a prognostic indicator of PTCs. Further investigation will need for the roles of miRNAs in the pathogenesis of papillary thyroid carcinomas.

Keyword

BRAF^V600E; mutation; MicroRNA; Papillary thyroid cancer

Figure

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  Fig. 1 Wild-type and mutant sequences of codon 600 of the BRAF gene.

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  Fig. 2 Levels of expression of miRNA in patients with papillary thyroid carcinoma (n = 42) and benign tumor (n = 9). #P = 0.00, as determined by the independent T-test, between the expression levels of miR-221 and miR-222 and miR-146b in papillary thyroid carcinoma and paired benign tumor.$ P = 0.00 by ANOVA between the expression levels of miR-221 and miR-222. &P = 0.00 (ANOVA) between the levels of expression of miR-221 and miR-146b.

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  Fig. 3 Relative quantification of miR-221, miR-222, and miR-146b in patients with papillary thyroid carcinoma or benign tumor. #P = 0.00, as quantified by independent T-test, between the levels of miR-146b in papillary thyroid carcinoma and paired benign tumor. $P = 0.00, when the expression of miR-221 and miR-146b were compared by ANOVA. &P = 0.00, when the levels of expression of miR-222 and miR-146b were compared by ANOVA.

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  Fig. 4 ROC curve analyses of (a) miR-221, (b) miR-222, and (c) miR-146b to help discriminate the patients with papillary thyroid carcinoma from those with benign tumor. The AUCs for miR-221, miR-222, and miR-146b were 0.762, 0.903, and 0.923, respectively.

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