Significance of the BRAF and RAS mRNA expression level in papillary thyroid carcinoma: An analysis of The Cancer Genome Atlas data

Abstract

Background and Aim BRAF and RAS mutations are the two most common mutations in papillary thyroid carcinoma (PTC), and BRAF mutation is associated with high-risk prognostic factors. However, the significance of the mRNA expression level of the two genes in PTC remains unknown. In this study, the significance of BRAF and RAS mRNA expression levels were investigated by analyzing PTC data from The Cancer Genome Atlas (TCGA) database. Methods Data from 499 patients were downloaded from the TCGA database. After excluding other PTC variants, total 353 cases of classic PTC, including 193 cases with BRAFV600E and 160 cases with the wild-type BRAF were selected. mRNA abundances were measured using RNA-Seq with the Expectation Maximization algorithm. Results None of the clinicopathological factors, including age, gender, thyroiditis, extrathyroidal extension, tumor size, AJCC stage, recurrence, or vital status, differed significantly between the BRAFV600E and wild-type BRAF patients. The mean BRAF mRNA level was significantly higher in BRAFV600E patients than in patients with wild-type BRAF (197.6 vs. 179.3, p = 0.031). In wild-type BRAF patients, the mean BRAF mRNA level was higher in cases with a tumor > 2 cm than those with a tumor ≤ 2.0 cm (189.4 vs. 163.8, p = 0.046), and was also higher in cases with lymph node metastasis than in those without lymph node metastasis (188.5 vs. 157.9, p =0.040). Within BRAFV600E patients, higher BRAF mRNA expression was associated with extrathyroidal extension (186.4 vs. 216.4, p = 0.001) and higher T stage (188.1 vs. 210.2, p =0.016). In BRAFV600E patients, higher NRAS mRNA expression count was associated with presence of thyroiditis (905.0 vs. 785.6, p = 0.001), extrathyroidal extension (921.6 vs. 826.5, p = 0.007), higher T stage (905.2 vs. 829.3, p = 0.024), and lymph node metastasis (906.0 vs. 822.0, p = 0.017). The mRNA expression count of KRAS was higher in the patients with extrathyroidal extension (738.8 vs. 647.9, p = 0.001), higher T stage (724.2 vs. 649.8, p = 0.005), lymph node metastasis (717.5 vs. 653.3, p = 0.018), and higher AJCC stage (721.9 vs. 661.9, p = 0.042). Conclusions A higher BRAF mRNA expression level was associated with tumor aggressiveness in classic PTC regardless of BRAF mutational status. NRAS and KRAS mutations were associated with tumor aggressiveness in BRAFV600E patients. Evaluation of BRAF and RAS mRNA level may be helpful in prognostic risk stratification of PTC.