Identification of prognostic biomarker in predicting hepatocarcinogenesis from cirrhotic liver using protein and gene signatures
- Authors
- Yim, Sun Young; Hae, Nahm Ji; Shin, Ji-Hyun; Jeong, Yun Seong; Kang, Sang-Hee; Park, Young Nyun; Um, Soon Ho; Lee, Ju-Seog
- Issue Date
- 12월-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://scholar.korea.ac.kr/handle/2021.sw.korea/61383
- 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.