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Cited 2 time in webofscience Cited 2 time in scopus
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Identification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures

Authors
Yim, Sun YoungHae, Nahm JiShin, Ji-HyunJeong, Yun SeongKang, Sang-HeePark, Young NyunUm, Soon HoLee, Ju-Seog
Issue Date
Dec-2019
Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
Keywords
Hepatocellular carcinoma; Liver cirrhosis; Caveolin-1; Reverse-phase protein array
Citation
EXPERIMENTAL AND MOLECULAR PATHOLOGY, v.111
Indexed
SCIE
SCOPUS
Journal Title
EXPERIMENTAL AND MOLECULAR PATHOLOGY
Volume
111
URI
https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/1338
DOI
10.1016/j.yexmp.2019.104319
ISSN
0014-4800
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.
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2. Clinical Science > Department of Colon and Rectal Surgery > 1. Journal Articles

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Kang, Sang hee
구로병원 (Department of Colon and Rectal Surgery, Guro Hospital)
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