Identification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures.
Exp Mol Pathol
; 111: 104319, 2019 12.
Article
em En
| MEDLINE
| ID: mdl-31676327
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 ANDMETHOD:
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 (nâ¯=â¯20) or low (nâ¯=â¯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 (Pâ¯<â¯.001). In a multivariate analysis, compared with other clinical variables, the PDLR-gene signature remained as a significant predictor of HCC (HR 1.904, Pâ¯=â¯.01). In vitro experiments revealed that compared with mock-transduced immortalized liver cells, CAV1-transduced cells showed significantly increased proliferation (Pâ¯<â¯.001) and colony formation in soft agar (Pâ¯<â¯.033). TMA with immunohistochemistry showed that tissues with CAV1 expression were more likely to develop HCC than tissues without CAV1 expression (Pâ¯=â¯.047).CONCLUSION:
CAV1 expression predicts HCC development, making it a potential biomarker and target for preventive therapy.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Carcinoma Hepatocelular
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Proliferação de Células
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Caveolina 1
/
Cirrose Hepática
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Neoplasias Hepáticas
/
Recidiva Local de Neoplasia
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Exp Mol Pathol
Ano de publicação:
2019
Tipo de documento:
Article