title: Significance of the BRAF mRNA Expression Level in Papillary Thyroid Carcinoma: An Analysis of The Cancer Genome Atlas Data.
abstract: BACKGROUND
  BRAFV600E is the most common mutation in papillary thyroid carcinoma (PTC), and it is associated with high-risk prognostic factors. However, the significance of the BRAF mRNA level in PTC remains unknown. We evaluated the significance of BRAF mRNA expression level 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, we selected 353 cases of classic PTC, including 193 cases with BRAFV600E and 160 cases with the wild-type BRAF. mRNA abundances were measured using RNA-Seq with the Expectation Maximization algorithm.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  A higher BRAF mRNA expression level was associated with tumor aggressiveness in classic PTC regardless of BRAF mutational status. Evaluation of BRAF mRNA level may be helpful in prognostic risk stratification of PTC.
authors.affiliation: Department of Surgery, Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul, 156-70, Korea.|Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Young Jun
authors.initials: YJ
authors.lastname: Chai
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Department of Surgery, Seoul National University Hospital and College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Jin Wook
authors.initials: JW
authors.lastname: Yi
authors.affiliation: Center for Chronic Disease, Research Institute, National Medical Center, Seoul, Korea.
authors.forename: Hyeon-Gun
authors.initials: HG
authors.lastname: Jee
authors.affiliation: Department of Pathology, Seoul National University Boramae Medical Center, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul, 156-70, Korea.
authors.forename: Young A
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Division of Biomedical Informatics, Systems Biomedical Informatics Research Center, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Ju Han
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Division of Endocrinology and Metabolism, Johns Hopkins University School of Medicine, 1830E Monument St, Ste 333, Baltimore, Maryland, 21287, United States of America.
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Xing
authors.affiliation: Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.|Department of Surgery, Seoul National University Hospital and College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Korea.
authors.forename: Kyu Eun
authors.initials: KE
authors.lastname: Lee
mesh_terms: D000328:Adult; D000368:Aged; D019943:Amino Acid Substitution / Q000235:genetics; D001271:Atlases as Topic; D002277:Carcinoma / Q000235:genetics* / Q000401:mortality; D002291:Carcinoma, Papillary; D030541:Databases, Genetic; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000401:mortality; D013966:Thyroiditis / Q000473:pathology
chemical_list: D012333:RNA, Messenger; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf