High-accuracy Detection of Preoperative Thyroid Nodules Using Combination of BRAF ^V600E Mutation and TMPRSS4 mRNA Level

Background: Papillary thyroid cancer (PTC) is the most common epithelial thyroid tumor, accounting for more than 80% of all thyroid cancers. Though the fine needle aspiration biopsy (FNAB) represents as the golden standard for the diagnostics of thyroid nodules, there is a ∼25% risk of indeterminate cytological features. TMPRSS4 is a newly found transmembrane serine protease which was overexpressed in papillary thyroid cancer (PTC). Aims: The aim of this study was to determine its potential as a diagnostic marker to improve the diagnostic accuracy of thyroid cancer. Methods: We used pyrosequencing and quantitative real-time PCR (qRT-PCT) approaches to examine BRAF ^V600E mutation and TMPRSS4 mRNA level in FNAB specimens of thyroid nodules. The detection and analysis were respectively applied to training group with 91, and test group with 88 samples. Results: We demonstrated that PTC patients had an increased TMPRSS4 mRNA level as compared with benign subjects. The diagnostic sensitivity, specificity, and accuracy of TMPRSS4 were 93.33, 100, and 96.70%, respectively. Notably, compared with BRAF ^V600E mutation testing alone, combining with TMPRSS4 mRNA level significantly increased the diagnostic sensitivity and accuracy. Conclusions: Our findings indicated BRAF ^V600E mutation combination with TMPRSS4 mRNA analysis can dramatically improve the sensitivity and accuracy of preoperative diagnosis of thyroid nodules.