Identification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures
DC Field | Value | Language |
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dc.contributor.author | Yim, Sun Young | - |
dc.contributor.author | Hae, Nahm Ji | - |
dc.contributor.author | Shin, Ji-Hyun | - |
dc.contributor.author | Jeong, Yun Seong | - |
dc.contributor.author | Kang, Sang-Hee | - |
dc.contributor.author | Park, Young Nyun | - |
dc.contributor.author | Um, Soon Ho | - |
dc.contributor.author | Lee, Ju-Seog | - |
dc.date.available | 2020-11-02T06:27:52Z | - |
dc.date.issued | 2019-12 | - |
dc.identifier.issn | 0014-4800 | - |
dc.identifier.issn | 1096-0945 | - |
dc.identifier.uri | https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/1338 | - |
dc.description.abstract | Introduction: 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.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Academic Press | - |
dc.title | Identification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1016/j.yexmp.2019.104319 | - |
dc.identifier.scopusid | 2-s2.0-85074375240 | - |
dc.identifier.wosid | 000499762900019 | - |
dc.identifier.bibliographicCitation | Experimental and Molecular Pathology, v.111 | - |
dc.citation.title | Experimental and Molecular Pathology | - |
dc.citation.volume | 111 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Pathology | - |
dc.relation.journalWebOfScienceCategory | Pathology | - |
dc.subject.keywordPlus | CAVEOLIN-1 | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.subject.keywordAuthor | Hepatocellular carcinoma | - |
dc.subject.keywordAuthor | Liver cirrhosis | - |
dc.subject.keywordAuthor | Caveolin-1 | - |
dc.subject.keywordAuthor | Reverse-phase protein array | - |
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