staging of biliary atresia at diagnosis by molecular profiling of the liver分段的胆道闭锁的诊断肝癌的分子分析.pdfVIP

Moyer et al. Genome Medicine 2010, 2:33 /content/2/5/33 R E S E A R C H Open Access Research Staging of biliary atresia at diagnosis by molecular profiling of the liver 1 6 2,5 1 1 1 Katie Moyer , Vivek Kaimal , Cristina Pacheco , Reena Mourya , Huan Xu , Pranavkumar Shivakumar , 3 3 4 2 6 6 Ranajit Chakraborty , Marepalli Rao , John C Magee , Kevin Bove , Bruce J Aronow , Anil G Jegga and Jorge A Bezerra* 1 Abstract Background: Young age at portoenterostomy has been linked to improved outcome in biliary atresia, but pre-existing biological factors may influence the rate of disease progression. In this study, we aimed to determine whether molecular profiling of the liver identifies stages of disease at diagnosis. Methods: We examined liver biopsies from 47 infants with biliary atresia enrolled in a prospective observational study. Biopsies were scored for inflammation and fibrosis, used for gene expression profiles, and tested for association with indicators of disease severity, response to surgery, and survival at 2 years. Results: Fourteen of 47 livers displayed predominant histological features of inflammation (N = 9) or fibrosis (N = 5), with the remainder showing similar levels of both simultaneously. By differential profiling of gene expression, the 14 livers had a unique molecular signature containing 150 gene probes. Applying prediction analysis models, the probes classified 29 of the remaining 33 livers into inflammation or fibrosis. Molecular classification into the two groups was validated by the findings of increased hepatic population of lymphocyte su