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

Authors
 Sun Young Yim  ;  Nahm Ji Hae  ;  Ji-Hyun Shin  ;  Yun Seong Jeong  ;  Sang-Hee Kang  ;  Young Nyun Park  ;  Soon Ho Um  ;  Ju-Seog Lee 
Citation
 EXPERIMENTAL AND MOLECULAR PATHOLOGY, Vol.111 : 104319, 2019-12 
Journal Title
 EXPERIMENTAL AND MOLECULAR PATHOLOGY 
ISSN
 0014-4800 
Issue Date
2019-12
MeSH
Biomarkers, Tumor / genetics ; Biomarkers, Tumor / metabolism* ; Carcinoma, Hepatocellular / diagnosis* ; Carcinoma, Hepatocellular / etiology ; Carcinoma, Hepatocellular / metabolism ; Caveolin 1 / genetics ; Caveolin 1 / metabolism* ; Cell Proliferation* ; Gene Expression Profiling ; Humans ; Liver Cirrhosis / complications* ; Liver Neoplasms / diagnosis* ; Liver Neoplasms / etiology ; Liver Neoplasms / metabolism ; Neoplasm Recurrence, Local / diagnosis* ; Neoplasm Recurrence, Local / etiology ; Neoplasm Recurrence, Local / metabolism ; Prognosis ; Protein Array Analysis ; Retrospective Studies ; Tumor Cells, Cultured
Keywords
Caveolin-1 ; Hepatocellular carcinoma ; Liver cirrhosis ; Reverse-phase protein array
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.
Full Text
https://www.sciencedirect.com/science/article/pii/S0014480019305490
DOI
10.1016/j.yexmp.2019.104319
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Nahm, Ji Hae(남지해) ORCID logo https://orcid.org/0000-0003-0902-866X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/181281
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