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Telomere length, TERT and shelterin complex proteins in hepatocellular carcinomas expressing ‘‘stemness’’-related markers

DC Field Value Language
dc.contributor.author박영년-
dc.contributor.author유정은-
dc.date.accessioned2014-12-18T09:07:37Z-
dc.date.available2014-12-18T09:07:37Z-
dc.date.issued2013-
dc.identifier.issn0168-8278-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/87584-
dc.description.abstractBACKGROUND & AIMS: Hepatocellular carcinomas (HCCs) expressing "stemness"-related markers have been associated with aggressive biological behavior and poor prognosis. We examined the relationship between "stemness"-related protein expression and telomere length, hTERT and shelterin complex protein expression and chromosomal instability. METHODS: Quantitative fluorescent in situ hybridization for telomere length, immunohistochemistry for K19, EpCAM, CD133, c-kit, HepPar1, hTERT, TRF1, TRF2, POT1, RAP1 and TPP1, and TUNEL assay were performed in 137 HCCs, and array comparative genomic hybridization was performed with 24 HCCs. RESULTS: Telomeres were significantly longer in HCCs expressing "stemness"-related proteins (K19: p < 0.001, EpCAM: p = 0.002, CD133: p = 0.002). On analyzing different tumor cells within EpCAM-expressing HCCs, EpCAM-positive tumor cells showed longer telomeres (1.329 ± 0.246) compared to EpCAM-negative tumor cells (0.996 ± 0.381) within the same HCCs (p = 0.031). Telomeres were significantly longer in HCCs expressing hTERT (p = 0.048) and RAP1 proteins (p = 0.031). K19-expressing HCCs expressed hTERT (p = 0.002), TRF2 (p = 0.001) and TPP1 (p = 0.013) more frequently compared to K19-negative HCCs. EpCAM-positivity was associated with more frequent hTERT (p = 0.028), TPP1 (p = 0.017), TRF2 (p = 0.027) and POT1 (p = 0.004) expression. Copy number alterations were more frequent in K19 and EpCAM-expressing HCCs compared to HCCs without these markers (K19: p = 0.038, EpCAM: p = 0.009). HCCs with longer telomeres were associated with a shorter overall (p = 0.019) and disease-free survivals (p = 0.049), and decreased disease-free survivals were seen in TRF2-positive HCCs (p = 0.018). CONCLUSIONS: HCCs expressing "stemness"-related proteins are characterized by increased telomere length, increased expression of hTERT and shelterin complex proteins, and increased chromosomal instability compared to conventional HCCs. Longer telomeres and TRF2 expression in HCCs are associated with poor patient outcomes.-
dc.description.statementOfResponsibilityopen-
dc.relation.isPartOfJOURNAL OF HEPATOLOGY-
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.MESHAged-
dc.subject.MESHAntigens, Neoplasm/metabolism-
dc.subject.MESHApoptosis-
dc.subject.MESHBiomarkers, Tumor/metabolism*-
dc.subject.MESHCarcinoma, Hepatocellular/genetics*-
dc.subject.MESHCarcinoma, Hepatocellular/metabolism*-
dc.subject.MESHCarcinoma, Hepatocellular/pathology-
dc.subject.MESHCell Adhesion Molecules/metabolism-
dc.subject.MESHCell Proliferation-
dc.subject.MESHChromosomal Instability-
dc.subject.MESHEpithelial Cell Adhesion Molecule-
dc.subject.MESHFemale-
dc.subject.MESHHumans-
dc.subject.MESHImmunohistochemistry-
dc.subject.MESHIn Situ Hybridization, Fluorescence-
dc.subject.MESHKeratin-19/metabolism-
dc.subject.MESHLiver Neoplasms/genetics*-
dc.subject.MESHLiver Neoplasms/metabolism*-
dc.subject.MESHLiver Neoplasms/pathology-
dc.subject.MESHMale-
dc.subject.MESHMiddle Aged-
dc.subject.MESHNeoplastic Stem Cells/metabolism-
dc.subject.MESHNeoplastic Stem Cells/pathology-
dc.subject.MESHPrognosis-
dc.subject.MESHTelomerase/metabolism*-
dc.subject.MESHTelomere Homeostasis/genetics-
dc.subject.MESHTelomere Homeostasis/physiology*-
dc.subject.MESHTelomere-Binding Proteins/metabolism*-
dc.subject.MESHTelomeric Repeat Binding Protein 2/metabolism-
dc.titleTelomere length, TERT and shelterin complex proteins in hepatocellular carcinomas expressing ‘‘stemness’’-related markers-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pathology (병리학)-
dc.contributor.googleauthorHaeryoung Kim-
dc.contributor.googleauthorJeong Eun Yoo-
dc.contributor.googleauthorJai Young Cho-
dc.contributor.googleauthorBong-Kyeong Oh-
dc.contributor.googleauthorYoo-Seok Yoon-
dc.contributor.googleauthorHo-Seong Han-
dc.contributor.googleauthorHye Seung Lee-
dc.contributor.googleauthorJa June Jang-
dc.contributor.googleauthorSook Hyang Jeong-
dc.contributor.googleauthorJin Wook Kim-
dc.contributor.googleauthorYoung Nyun Park-
dc.identifier.doi10.1016/j.jhep.2013.05.011-
dc.admin.authorfalse-
dc.admin.mappingfalse-
dc.contributor.localIdA02504-
dc.contributor.localIdA01563-
dc.relation.journalcodeJ01441-
dc.identifier.eissn1600-0641-
dc.identifier.pmid23685049-
dc.identifier.urlhttp://www.sciencedirect.com/science/article/pii/S0168827813003371-
dc.subject.keywordHepatocellular carcinoma-
dc.subject.keywordStemness-
dc.subject.keywordTelomere-
dc.subject.keywordTERT-
dc.subject.keywordShelterin-
dc.contributor.alternativeNamePark, Young Nyun-
dc.contributor.alternativeNameYoo, Jeong Eun-
dc.contributor.affiliatedAuthorYoo, Jeong Eun-
dc.contributor.affiliatedAuthorPark, Young Nyun-
dc.rights.accessRightsnot free-
dc.citation.volume59-
dc.citation.number4-
dc.citation.startPage746-
dc.citation.endPage752-
dc.identifier.bibliographicCitationJOURNAL OF HEPATOLOGY, Vol.59(4) : 746-752, 2013-
dc.identifier.rimsid34330-
dc.type.rimsART-
Appears in Collections:
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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