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Aberrant expression of COT is related to recurrence of papillary thyroid cancer

DC FieldValueLanguage
dc.contributor.author강상욱-
dc.contributor.author구철룡-
dc.contributor.author남기현-
dc.contributor.author신동엽-
dc.contributor.author이은직-
dc.contributor.author이잔디-
dc.contributor.author이초록-
dc.contributor.author정선향-
dc.contributor.author정웅윤-
dc.contributor.author정종주-
dc.contributor.author조영석-
dc.date.accessioned2016-02-04T10:59:19Z-
dc.date.available2016-02-04T10:59:19Z-
dc.date.issued2015-
dc.identifier.issn0025-7974-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/139419-
dc.description.abstractAberrant expression of Cancer Osaka Thyroid Oncogene mitogen-activated protein kinase kinase kinase 8 (COT) (MAP3K8) is a driver of resistance to B-RAF inhibition. However, the de novo expression and clinical implications of COT in papillary thyroid cancer (PTC) have not been investigated.The aim of this study is to investigate the expression of A-, B-, C-RAF, and COT in PTC (n = 167) and analyze the clinical implications of aberrant expression of these genes.Quantitative polymerase chain reaction (qPCR) and immunohistochemical staining (IHC) were performed on primary thyroid cancers. Expression of COT was compared with clinicopathological characteristics including recurrence-free survival. Datasets from public repository (NCBI) were subjected to Gene Set Enrichment Analysis (GSEA).qPCR data showed that the relative mRNA expression of A-, B-, C-RAF and COT of PTC were higher than normal tissues (all P < 0.01). In addition, the expression of COT mRNA in PTC showed positive correlation with A- (r = 0.4083, P < 0.001), B- (r = 0.2773, P = 0.0003), and C-RAF (r = 0.5954, P < 0.001). The mRNA expressions of A-, B,- and C-RAF were also correlated with each other (all P < 0.001). In IHC, the staining intensities of B-RAF and COT were higher in PTC than in normal tissue (P < 0.001). Interestingly, moderate-to-strong staining intensities of B-RAF and COT were more frequent in B-RAF-positive PTC (P < 0.001, P = 0.013, respectively). In addition, aberrant expression of COT was related to old age at initial diagnosis (P = 0.045) and higher recurrence rate (P = 0.025). In multivariate analysis, tumor recurrence was persistently associated with moderate-to-strong staining of COT after adjusting for age, sex, extrathyroidal extension, multifocality, T-stage, N-stage, TNM stage, and B-RAF mutation (odds ratio, 4.662; 95% confidence interval 1.066 - 21.609; P = 0.045). Moreover, moderate-to-strong COT expression in PTC was associated with shorter recurrence-free survival (mean follow-up duration, 14.2 ± 4.1 years; P = 0.0403). GSEA indicated that gene sets related to B-RAF-RAS (P < 0.0001, false discovery rate [FDR] q-value = 0.000) and thyroid differentiation (P = 0.048, FDR q-value = 0.05) scores were enriched in lower COT expression group and gene sets such as T-cell receptor signaling pathway and Toll-like receptor signaling pathway are coordinately upregulated in higher COT expression group (both, P < 0.0001, FDR q-value = 0.000).Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC.-
dc.description.statementOfResponsibilityopen-
dc.format.extente548-
dc.relation.isPartOfMEDICINE-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/2.0/kr/-
dc.subject.MESHAdult-
dc.subject.MESHAge Factors-
dc.subject.MESHBlotting, Western-
dc.subject.MESHCarcinoma, Papillary/genetics*-
dc.subject.MESHCarcinoma, Papillary/mortality-
dc.subject.MESHDNA/analysis-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHImmunohistochemistry-
dc.subject.MESHMAP Kinase Kinase Kinases/genetics*-
dc.subject.MESHMale-
dc.subject.MESHNeoplasm Recurrence, Local/genetics*-
dc.subject.MESHProto-Oncogene Proteins/genetics*-
dc.subject.MESHProto-Oncogene Proteins A-raf/genetics*-
dc.subject.MESHProto-Oncogene Proteins B-raf/genetics*-
dc.subject.MESHProto-Oncogene Proteins c-raf/genetics*-
dc.subject.MESHRNA, Messenger/analysis-
dc.subject.MESHReal-Time Polymerase Chain Reaction-
dc.subject.MESHThyroid Neoplasms/genetics*-
dc.subject.MESHThyroid Neoplasms/mortality-
dc.titleAberrant expression of COT is related to recurrence of papillary thyroid cancer-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Internal Medicine (내과학)-
dc.contributor.googleauthorJandee Lee-
dc.contributor.googleauthorSeonhyang Jeong-
dc.contributor.googleauthorJae Hyun Park-
dc.contributor.googleauthorCho Rok Lee-
dc.contributor.googleauthorCheol Ryong Ku-
dc.contributor.googleauthorSang-Wook Kang-
dc.contributor.googleauthorJong Ju Jeong-
dc.contributor.googleauthorKee-Hyun Nam-
dc.contributor.googleauthorDong Yeob Shin-
dc.contributor.googleauthorEun Jig Lee-
dc.contributor.googleauthorWoong Youn Chung-
dc.contributor.googleauthorYoung Suk Jo-
dc.identifier.doi10.1097/MD.0000000000000548-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA00032-
dc.contributor.localIdA00201-
dc.contributor.localIdA01245-
dc.contributor.localIdA02093-
dc.contributor.localIdA03050-
dc.contributor.localIdA03066-
dc.contributor.localIdA03256-
dc.contributor.localIdA03621-
dc.contributor.localIdA03674-
dc.contributor.localIdA03722-
dc.contributor.localIdA03853-
dc.relation.journalcodeJ02214-
dc.identifier.eissn1536-5964-
dc.identifier.pmid25674762-
dc.contributor.alternativeNameKang, Sang Wook-
dc.contributor.alternativeNameKu, Cheol Ryong-
dc.contributor.alternativeNameNam, Kee Hyun-
dc.contributor.alternativeNameShin, Dong Yeob-
dc.contributor.alternativeNameLee, Eun Jig-
dc.contributor.alternativeNameLee, Jan Dee-
dc.contributor.alternativeNameLee, Cho Rok-
dc.contributor.alternativeNameJeong, Seon Hyang-
dc.contributor.alternativeNameChung, Woung Youn-
dc.contributor.alternativeNameJeong, Jong Ju-
dc.contributor.alternativeNameJo, Young Suk-
dc.contributor.affiliatedAuthorKang, Sang Wook-
dc.contributor.affiliatedAuthorKu, Cheol Ryong-
dc.contributor.affiliatedAuthorNam, Kee Hyun-
dc.contributor.affiliatedAuthorShin, Dong Yeob-
dc.contributor.affiliatedAuthorLee, Eun Jig-
dc.contributor.affiliatedAuthorLee, Jan Dee-
dc.contributor.affiliatedAuthorLee, Cho Rok-
dc.contributor.affiliatedAuthorJeong, Seon Hyang-
dc.contributor.affiliatedAuthorChung, Woung Youn-
dc.contributor.affiliatedAuthorJeong, Jong Ju-
dc.contributor.affiliatedAuthorJo, Young Suk-
dc.rights.accessRightsfree-
dc.citation.volume94-
dc.citation.number6-
dc.citation.startPage548-
dc.identifier.bibliographicCitationMEDICINE, Vol.94(6) : 548, 2015-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers

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