RESUMEN
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 (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.