Cited 3 times in
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 | 남지해 | - |
dc.contributor.author | 박영년 | - |
dc.date.accessioned | 2021-01-19T07:39:52Z | - |
dc.date.available | 2021-01-19T07:39:52Z | - |
dc.date.issued | 2019-12 | - |
dc.identifier.issn | 0014-4800 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/181281 | - |
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.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Elsevier | - |
dc.relation.isPartOf | EXPERIMENTAL AND MOLECULAR PATHOLOGY | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Biomarkers, Tumor / genetics | - |
dc.subject.MESH | Biomarkers, Tumor / metabolism* | - |
dc.subject.MESH | Carcinoma, Hepatocellular / diagnosis* | - |
dc.subject.MESH | Carcinoma, Hepatocellular / etiology | - |
dc.subject.MESH | Carcinoma, Hepatocellular / metabolism | - |
dc.subject.MESH | Caveolin 1 / genetics | - |
dc.subject.MESH | Caveolin 1 / metabolism* | - |
dc.subject.MESH | Cell Proliferation* | - |
dc.subject.MESH | Gene Expression Profiling | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Liver Cirrhosis / complications* | - |
dc.subject.MESH | Liver Neoplasms / diagnosis* | - |
dc.subject.MESH | Liver Neoplasms / etiology | - |
dc.subject.MESH | Liver Neoplasms / metabolism | - |
dc.subject.MESH | Neoplasm Recurrence, Local / diagnosis* | - |
dc.subject.MESH | Neoplasm Recurrence, Local / etiology | - |
dc.subject.MESH | Neoplasm Recurrence, Local / metabolism | - |
dc.subject.MESH | Prognosis | - |
dc.subject.MESH | Protein Array Analysis | - |
dc.subject.MESH | Retrospective Studies | - |
dc.subject.MESH | Tumor Cells, Cultured | - |
dc.title | Identification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Pathology (병리학교실) | - |
dc.contributor.googleauthor | Sun Young Yim | - |
dc.contributor.googleauthor | Nahm Ji Hae | - |
dc.contributor.googleauthor | Ji-Hyun Shin | - |
dc.contributor.googleauthor | Yun Seong Jeong | - |
dc.contributor.googleauthor | Sang-Hee Kang | - |
dc.contributor.googleauthor | Young Nyun Park | - |
dc.contributor.googleauthor | Soon Ho Um | - |
dc.contributor.googleauthor | Ju-Seog Lee | - |
dc.identifier.doi | 10.1016/j.yexmp.2019.104319 | - |
dc.contributor.localId | A05120 | - |
dc.relation.journalcode | J00861 | - |
dc.identifier.eissn | 1096-0945 | - |
dc.identifier.pmid | 31676327 | - |
dc.identifier.url | https://www.sciencedirect.com/science/article/pii/S0014480019305490 | - |
dc.subject.keyword | Caveolin-1 | - |
dc.subject.keyword | Hepatocellular carcinoma | - |
dc.subject.keyword | Liver cirrhosis | - |
dc.subject.keyword | Reverse-phase protein array | - |
dc.contributor.alternativeName | Nahm, Ji Hae | - |
dc.contributor.affiliatedAuthor | 남지해 | - |
dc.citation.volume | 111 | - |
dc.citation.startPage | 104319 | - |
dc.identifier.bibliographicCitation | EXPERIMENTAL AND MOLECULAR PATHOLOGY, Vol.111 : 104319, 2019-12 | - |
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