molecular profiles of hcv cirrhotic tissues derived in a panel of markers with clinical utility for hepatocellular carcinoma surveillance分子的丙肝肝硬化组织派生的面板标记与肝细胞癌的临床效用监测.pdfVIP

Molecular Profiles of HCV Cirrhotic Tissues Derived in a Panel of Markers with Clinical Utility for Hepatocellular Carcinoma Surveillance 1 2,3 1. 1 . Ricardo C. Gehrau , Kellie J. Archer , Valeria R. Mas , Daniel G. Maluf * 1 University of Virginia, Department of Surgery, Transplant Division. Charlottesville, Virginia, United States of America, 2 Virginia Commonwealth University, Department of Biostatistics. Richmond, Virginia, United States of America, 3 Massey Cancer Center, Biostatistics Shared Resource. Richmond, Virginia, United States of America Abstract Background: Early hepatocellular carcinoma (HCC) detection is difficult because low accuracy of surveillance tests. Genome- wide analyses were performed using HCV-cirrhosis with HCC to identify predictive signatures. Methodology/Principal Findings: Cirrhotic liver tissue was collected from 107 HCV-infected patients with diagnosis of HCC at pre-transplantation and confirmed in explanted livers. Study groups included: 1) microarray hybridization set (n = 80) including patients without (woHCC = 45) and with (wHCC = 24) HCC, and with incidental HCC (iHCC = 11); 2) independent validation set (n = 27; woHCC = 16, wHCC = 11). Pairwise comparisons were performed using moderated t-test. FDR,1% was considered significant. L1-penalized logistic regression model was fit for woHCC and wHCC microarrays, and tested against iHCC. Prediction model genes were validated in independent set by qPCR. The genomic profile was associated with genetic disorders and cancer focused on gene expression, cell cycle and cell death. Molecular profile analysis revealed cell cycle progression and arrest at G2/M, but progressing to mitosis; unregulated DNA damage check-points, and apoptosis. The prediction m