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Identification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures

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dc.contributor.author남지해-
dc.date.accessioned2021-01-19T07:39:52Z-
dc.date.available2021-01-19T07:39:52Z-
dc.date.issued2019-12-
dc.identifier.issn0014-4800-
dc.identifier.urihttps://ir.ymlib.yonsei.ac.kr/handle/22282913/181281-
dc.description.abstractIntroduction: Cirrhosis primes the liver for hepatocellular carcinoma (HCC) development. However, biomarkers that predict HCC in cirrhosis patients are lacking. Thus, we aimed to identify a biomarker directly from protein analysis and relate it with transcriptomic data to validate in larger cohorts. Material and method: Forty-six patients who underwent hepatectomy for HCC that arose from cirrhotic liver were enrolled. Reverse-phase protein array and microarray data of these patients were analyzed. Clinical validation was performed in two independent cohorts and functional validation using cell and tissue microarray (TMA). Results: Systematic analysis performed after selecting 20 proteins from 201 proteins with AUROC >70 effectively categorized patients into high (n = 20) or low (n = 26) risk HCC groups. Proteome-derived late recurrence (PDLR)-gene signature comprising 298 genes that significantly differed between high and low risk groups predicted HCC well in a cohort of 216 cirrhosis patients and also de novo HCC recurrence in a cohort of 259 patients who underwent hepatectomy. Among 20 proteins that were selected for analysis, caveolin-1 (CAV1) was the most dominant protein that categorized the patients into high and low risk groups (P < .001). In a multivariate analysis, compared with other clinical variables, the PDLR-gene signature remained as a significant predictor of HCC (HR 1.904, P = .01). In vitro experiments revealed that compared with mock-transduced immortalized liver cells, CAV1-transduced cells showed significantly increased proliferation (P < .001) and colony formation in soft agar (P < .033). TMA with immunohistochemistry showed that tissues with CAV1 expression were more likely to develop HCC than tissues without CAV1 expression (P = .047). Conclusion: CAV1 expression predicts HCC development, making it a potential biomarker and target for preventive therapy.-
dc.description.statementOfResponsibilityrestriction-
dc.languageEnglish-
dc.publisherElsevier-
dc.relation.isPartOfEXPERIMENTAL AND MOLECULAR PATHOLOGY-
dc.rightsCC BY-NC-ND 2.0 KR-
dc.subject.MESHBiomarkers, Tumor / genetics-
dc.subject.MESHBiomarkers, Tumor / metabolism*-
dc.subject.MESHCarcinoma, Hepatocellular / diagnosis*-
dc.subject.MESHCarcinoma, Hepatocellular / etiology-
dc.subject.MESHCarcinoma, Hepatocellular / metabolism-
dc.subject.MESHCaveolin 1 / genetics-
dc.subject.MESHCaveolin 1 / metabolism*-
dc.subject.MESHCell Proliferation*-
dc.subject.MESHGene Expression Profiling-
dc.subject.MESHHumans-
dc.subject.MESHLiver Cirrhosis / complications*-
dc.subject.MESHLiver Neoplasms / diagnosis*-
dc.subject.MESHLiver Neoplasms / etiology-
dc.subject.MESHLiver Neoplasms / metabolism-
dc.subject.MESHNeoplasm Recurrence, Local / diagnosis*-
dc.subject.MESHNeoplasm Recurrence, Local / etiology-
dc.subject.MESHNeoplasm Recurrence, Local / metabolism-
dc.subject.MESHPrognosis-
dc.subject.MESHProtein Array Analysis-
dc.subject.MESHRetrospective Studies-
dc.subject.MESHTumor Cells, Cultured-
dc.titleIdentification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures-
dc.typeArticle-
dc.contributor.collegeCollege of Medicine (의과대학)-
dc.contributor.departmentDept. of Pathology (병리학교실)-
dc.contributor.googleauthorSun Young Yim-
dc.contributor.googleauthorNahm Ji Hae-
dc.contributor.googleauthorJi-Hyun Shin-
dc.contributor.googleauthorYun Seong Jeong-
dc.contributor.googleauthorSang-Hee Kang-
dc.contributor.googleauthorYoung Nyun Park-
dc.contributor.googleauthorSoon Ho Um-
dc.contributor.googleauthorJu-Seog Lee-
dc.identifier.doi10.1016/j.yexmp.2019.104319-
dc.contributor.localIdA05120-
dc.relation.journalcodeJ00861-
dc.identifier.eissn1096-0945-
dc.identifier.pmid31676327-
dc.identifier.urlhttps://www.sciencedirect.com/science/article/pii/S0014480019305490-
dc.subject.keywordCaveolin-1-
dc.subject.keywordHepatocellular carcinoma-
dc.subject.keywordLiver cirrhosis-
dc.subject.keywordReverse-phase protein array-
dc.contributor.alternativeNameNahm, Ji Hae-
dc.contributor.affiliatedAuthor남지해-
dc.citation.volume111-
dc.citation.startPage104319-
dc.identifier.bibliographicCitationEXPERIMENTAL AND MOLECULAR PATHOLOGY, Vol.111 : 104319, 2019-12-
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers

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