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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.authorYim, Sun Young-
dc.contributor.authorHae, Nahm Ji-
dc.contributor.authorShin, Ji-Hyun-
dc.contributor.authorJeong, Yun Seong-
dc.contributor.authorKang, Sang-Hee-
dc.contributor.authorPark, Young Nyun-
dc.contributor.authorUm, Soon Ho-
dc.contributor.authorLee, Ju-Seog-
dc.date.available2020-11-02T06:27:52Z-
dc.date.issued2019-12-
dc.identifier.issn0014-4800-
dc.identifier.issn1096-0945-
dc.identifier.urihttps://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/1338-
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.language영어-
dc.language.isoENG-
dc.publisherACADEMIC PRESS INC ELSEVIER SCIENCE-
dc.titleIdentification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures-
dc.typeArticle-
dc.publisher.location미국-
dc.identifier.doi10.1016/j.yexmp.2019.104319-
dc.identifier.scopusid2-s2.0-85074375240-
dc.identifier.wosid000499762900019-
dc.identifier.bibliographicCitationEXPERIMENTAL AND MOLECULAR PATHOLOGY, v.111-
dc.citation.titleEXPERIMENTAL AND MOLECULAR PATHOLOGY-
dc.citation.volume111-
dc.type.docTypeArticle-
dc.description.isOpenAccessN-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaPathology-
dc.relation.journalWebOfScienceCategoryPathology-
dc.subject.keywordPlusCAVEOLIN-1-
dc.subject.keywordPlusEXPRESSION-
dc.subject.keywordAuthorHepatocellular carcinoma-
dc.subject.keywordAuthorLiver cirrhosis-
dc.subject.keywordAuthorCaveolin-1-
dc.subject.keywordAuthorReverse-phase protein array-
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2. Clinical Science > Department of Gastroenterology and Hepatology > 1. Journal Articles
2. Clinical Science > Department of Colon and Rectal Surgery > 1. Journal Articles

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