{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:34:25Z","timestamp":1773272065474,"version":"3.50.1"},"reference-count":47,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T00:00:00Z","timestamp":1468368000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004082","name":"Korean Foundation for Cancer Research","doi-asserted-by":"publisher","award":["CB-2011-03-01"],"award-info":[{"award-number":["CB-2011-03-01"]}],"id":[{"id":"10.13039\/501100004082","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003625","name":"Ministry of Health and Welfare","doi-asserted-by":"publisher","award":["HI13C2164"],"award-info":[{"award-number":["HI13C2164"]}],"id":[{"id":"10.13039\/501100003625","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0159235","type":"journal-article","created":{"date-parts":[[2016,7,13]],"date-time":"2016-07-13T20:02:22Z","timestamp":1468440142000},"page":"e0159235","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":16,"title":["Significance of the BRAF mRNA Expression Level in Papillary Thyroid Carcinoma: An Analysis of The Cancer Genome Atlas Data"],"prefix":"10.1371","volume":"11","author":[{"given":"Young Jun","family":"Chai","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin Wook","family":"Yi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeon-Gun","family":"Jee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young A","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Han","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingzhao","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyu Eun","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2016,7,13]]},"reference":[{"issue":"1","key":"ref1","first-page":"9","article-title":"Cancer statistics, 2014","volume":"64","author":"R Siegel","year":"2014","journal-title":"CA: a cancer journal for clinicians"},{"issue":"18","key":"ref2","doi-asserted-by":"crossref","first-page":"2164","DOI":"10.1001\/jama.295.18.2164","article-title":"Increasing incidence of thyroid cancer in the United States, 1973\u20132002","volume":"295","author":"L Davies","year":"2006","journal-title":"JAMA: the journal of the American Medical Association"},{"issue":"12","key":"ref3","doi-asserted-by":"crossref","first-page":"6373","DOI":"10.1210\/jc.2005-0987","article-title":"BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer","volume":"90","author":"M Xing","year":"2005","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"1","key":"ref4","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1200\/JCO.2014.56.8253","article-title":"Association Between BRAF V600E Mutation and Recurrence of Papillary Thyroid Cancer","volume":"33","author":"M Xing","year":"2015","journal-title":"Journal of clinical oncology: official journal of the American Society of Clinical Oncology"},{"issue":"2","key":"ref5","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1210\/jc.2007-1717","article-title":"Clinicopathological analysis of papillary thyroid cancer with PIK3CA alterations in a Middle Eastern population","volume":"93","author":"J Abubaker","year":"2008","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"2","key":"ref6","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1530\/ERC-13-0291","article-title":"Is BRAFV600E mutation a marker for central nodal metastasis in small papillary thyroid carcinoma?","volume":"21","author":"BH Lang","year":"2014","journal-title":"Endocrine-related cancer"},{"issue":"7","key":"ref7","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1210\/er.2007-0007","article-title":"BRAF mutation in papillary thyroid cancer: pathogenic role, molecular bases, and clinical implications","volume":"28","author":"M Xing","year":"2007","journal-title":"Endocrine reviews"},{"issue":"7","key":"ref8","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1002\/cncr.26500","article-title":"The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis","volume":"118","author":"TH Kim","year":"2012","journal-title":"Cancer"},{"issue":"2","key":"ref9","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1677\/erc.1.0978","article-title":"BRAF mutation in thyroid cancer","volume":"12","author":"M Xing","year":"2005","journal-title":"Endocrine-related cancer"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.mce.2009.10.012","article-title":"Prognostic utility of BRAF mutation in papillary thyroid cancer","volume":"321","author":"M Xing","year":"2010","journal-title":"Molecular and cellular endocrinology"},{"issue":"6","key":"ref11","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1111\/cen.12386","article-title":"The BRAF(V600E) mutation in papillary thyroid microcarcinoma: does the mutation have an impact on clinical outcome?","volume":"80","author":"A Walczyk","year":"2014","journal-title":"Clinical endocrinology"},{"issue":"1","key":"ref12","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1507\/endocrj.K08E-208","article-title":"BRAF mutation in papillary thyroid carcinoma in a Japanese population: its lack of correlation with high-risk clinicopathological features and disease-free survival of patients","volume":"56","author":"Y Ito","year":"2009","journal-title":"Endocrine journal"},{"issue":"6","key":"ref13","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/j.surg.2013.06.020","article-title":"Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma","volume":"154","author":"J Zagzag","year":"2013","journal-title":"Surgery"},{"issue":"6","key":"ref14","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1530\/ERC-14-0147","article-title":"Quantification of BRAF V600E alleles predicts papillary thyroid cancer progression","volume":"21","author":"MH Kim","year":"2014","journal-title":"Endocrine-related cancer"},{"issue":"7","key":"ref15","doi-asserted-by":"crossref","first-page":"2333","DOI":"10.1210\/jc.2011-3106","article-title":"A high percentage of BRAFV600E alleles in papillary thyroid carcinoma predicts a poorer outcome","volume":"97","author":"A Guerra","year":"2012","journal-title":"The Journal of clinical endocrinology and metabolism"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"B Li","year":"2011","journal-title":"BMC Bioinformatics"},{"issue":"3","key":"ref17","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.cell.2014.09.050","article-title":"Integrated genomic characterization of papillary thyroid carcinoma","volume":"159","year":"2014","journal-title":"Cell"},{"issue":"6","key":"ref18","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/j.surg.2014.08.050","article-title":"Expression of the embryonic morphogen Nodal in differentiated thyroid carcinomas: Immunohistochemistry assay in tissue microarray and The Cancer Genome Atlas data analysis","volume":"156","author":"YJ Chai","year":"2014","journal-title":"Surgery"},{"issue":"8","key":"ref19","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.4161\/cc.9.8.11487","article-title":"Dominant roles of the Raf\/MEK\/ERK pathway in cell cycle progression, prevention of apoptosis and sensitivity to chemotherapeutic drugs","volume":"9","author":"LS Steelman","year":"2010","journal-title":"Cell Cycle"},{"issue":"7","key":"ref20","first-page":"1454","article-title":"High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET\/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma","volume":"63","author":"ET Kimura","year":"2003","journal-title":"Cancer research"},{"issue":"6892","key":"ref21","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1038\/nature00766","article-title":"Mutations of the BRAF gene in human cancer","volume":"417","author":"H Davies","year":"2002","journal-title":"Nature"},{"issue":"6","key":"ref22","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/S0092-8674(04)00215-6","article-title":"Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF","volume":"116","author":"PT Wan","year":"2004","journal-title":"Cell"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"10775","DOI":"10.1038\/srep10775","article-title":"Relationship between differentially expressed mRNA and mRNA-protein correlations in a xenograft model system","volume":"5","author":"A Koussounadis","year":"2015","journal-title":"Sci Rep"},{"issue":"5","key":"ref24","doi-asserted-by":"crossref","first-page":"e1005206","DOI":"10.1371\/journal.pgen.1005206","article-title":"Accounting for experimental noise reveals that mRNA levels, amplified by post-transcriptional processes, largely determine steady-state protein levels in yeast","volume":"11","author":"G Csardi","year":"2015","journal-title":"PLoS Genet"},{"issue":"4","key":"ref25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/nrg3185","article-title":"Insights into the regulation of protein abundance from proteomic and transcriptomic analyses","volume":"13","author":"C Vogel","year":"2012","journal-title":"Nat Rev Genet"},{"issue":"8","key":"ref26","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.prp.2012.05.013","article-title":"mRNA BRAF expression helps to identify papillary thyroid carcinomas in thyroid nodules independently of the presence of BRAFV600E mutation","volume":"208","author":"PP Araujo","year":"2012","journal-title":"Pathology, research and practice"},{"issue":"3","key":"ref27","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1089\/thy.2015.0315","article-title":"An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC\/UICC Staging System for Well-Differentiated Thyroid Cancer","volume":"26","author":"IJ Nixon","year":"2016","journal-title":"Thyroid"},{"issue":"14","key":"ref28","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1001\/jama.2013.3190","article-title":"Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer","volume":"309","author":"M Xing","year":"2013","journal-title":"JAMA: the journal of the American Medical Association"},{"issue":"4","key":"ref29","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1016\/j.amjsurg.2011.02.013","article-title":"Is the BRAF(V600E) mutation useful as a predictor of preoperative risk in papillary thyroid cancer?","volume":"203","author":"JK Nam","year":"2012","journal-title":"Am J Surg"},{"issue":"2","key":"ref30","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.anl.2011.07.011","article-title":"BRAFV600E mutation does not serve as a prognostic factor in Korean patients with papillary thyroid carcinoma","volume":"39","author":"D Ahn","year":"2012","journal-title":"Auris, nasus, larynx"},{"key":"ref31","article-title":"BRAFV600E mutation in papillary thyroid microcarcinoma: a meta-analysis","author":"F Li","year":"2015","journal-title":"Endocrine-related cancer"},{"issue":"6","key":"ref32","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1097\/PAS.0b013e318246b527","article-title":"Immunohistochemical detection of the BRAF V600E-mutated protein in papillary thyroid carcinoma","volume":"36","author":"O Koperek","year":"2012","journal-title":"The American journal of surgical pathology"},{"issue":"1","key":"ref33","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1002\/cncy.21352","article-title":"Value of immunohistochemistry in the detection of BRAF(V600E) mutations in fine-needle aspiration biopsies of papillary thyroid carcinoma","volume":"122","author":"AK Zimmermann","year":"2014","journal-title":"Cancer cytopathology"},{"issue":"5","key":"ref34","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1055\/s-0034-1368700","article-title":"Immunohistochemistry for BRAF(V600E) antibody VE1 performed in core needle biopsy samples identifies mutated papillary thyroid cancers","volume":"46","author":"A Crescenzi","year":"2014","journal-title":"Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme"},{"issue":"5","key":"ref35","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1089\/thy.2013.0302","article-title":"Diagnostic value of immunohistochemistry for the detection of the BRAF(V600E) mutation in papillary thyroid carcinoma: comparative analysis with three DNA-based assays","volume":"24","author":"MI Ilie","year":"2014","journal-title":"Thyroid"},{"issue":"2","key":"ref36","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/bjd.12351","article-title":"Disease progression and patient survival are significantly influenced by BRAF protein expression in primary melanoma","volume":"169","author":"G Safaee Ardekani","year":"2013","journal-title":"The British journal of dermatology"},{"issue":"8","key":"ref37","doi-asserted-by":"crossref","first-page":"E1414","DOI":"10.1210\/jc.2013-1408","article-title":"Immunohistochemical detection of mutated BRAF V600E supports the clonal origin of BRAF-induced thyroid cancers along the spectrum of disease progression","volume":"98","author":"RA Ghossein","year":"2013","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"2","key":"ref38","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1210\/jc.2011-0618","article-title":"The primary occurrence of BRAF(V600E) is a rare clonal event in papillary thyroid carcinoma","volume":"97","author":"A Guerra","year":"2012","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"Suppl 4","key":"ref39","doi-asserted-by":"crossref","first-page":"S619","DOI":"10.1245\/s10434-014-3723-5","article-title":"Significance of allelic percentage of BRAF c.1799T > A (V600E) mutation in papillary thyroid carcinoma","volume":"21","author":"SP Cheng","year":"2014","journal-title":"Annals of surgical oncology"},{"issue":"4","key":"ref40","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1210\/jc.2015-4031","article-title":"Subclonality for BRAF Mutation in Papillary Thyroid Carcinoma Is Associated With Earlier Disease Stage","volume":"101","author":"A Finkel","year":"2016","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"8","key":"ref41","doi-asserted-by":"crossref","first-page":"E1530","DOI":"10.1210\/jc.2013-4389","article-title":"High-sensitivity BRAF mutation analysis: BRAF V600E is acquired early during tumor development but is heterogeneously distributed in a subset of papillary thyroid carcinomas","volume":"99","author":"D de Biase","year":"2014","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"12","key":"ref42","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.humpath.2007.04.014","article-title":"Enhanced B-Raf protein expression is independent of V600E mutant status in thyroid carcinomas","volume":"38","author":"T Kondo","year":"2007","journal-title":"Human pathology"},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1210\/en.2005-0280","article-title":"BRAF mediates RET\/PTC-induced mitogen-activated protein kinase activation in thyroid cells: functional support for requirement of the RET\/PTC-RAS-BRAF pathway in papillary thyroid carcinogenesis","volume":"147","author":"N Mitsutake","year":"2006","journal-title":"Endocrinology"},{"issue":"6","key":"ref44","doi-asserted-by":"crossref","first-page":"1785","DOI":"10.1158\/1078-0432.CCR-05-1729","article-title":"Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET\/PTC or BRAF mutations in vitro and in vivo","volume":"12","author":"B Ouyang","year":"2006","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"issue":"7","key":"ref45","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1210\/jc.2012-2201","article-title":"BRAFV600E mutation and papillary thyroid cancer: chicken or egg?","volume":"97","author":"M Xing","year":"2012","journal-title":"The Journal of clinical endocrinology and metabolism"},{"issue":"7377","key":"ref46","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/nature10662","article-title":"RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)","volume":"480","author":"PI Poulikakos","year":"2011","journal-title":"Nature"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1038\/ncomms1727","article-title":"Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance","volume":"3","author":"H Shi","year":"2012","journal-title":"Nature communications"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0159235","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T23:52:11Z","timestamp":1568159531000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0159235"}},"subtitle":[],"editor":[{"given":"Paula","family":"Soares","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2016,7,13]]},"references-count":47,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7,13]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0159235","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,13]]}}}