Volume 67, Issue 1, pages 86–96, January 2018
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1 INSERM U948, Institut des Maladies de l'Appareil Digestif, CHU de Nantes, France
2 INSERM U1193, Paris-Sud University, Paul Brousse Hospital, Villejuif, France
3 Unité Hepacivirus et Immunité Innée, CNRS URA 3015, Institut Pasteur, Paris, France
4 INSERM U955, Paris-Est-Créteil University, Henri Mondor Hospital, Créteil, France
5 Pathology Department, CHU Bordeaux, INSERM U1053, Bordeaux 2 University, Bordeaux, France
*ADDRESS CORRESPONDENCE AND REPRINT REQUESTS:
Cyrille Féray, M.D., Ph.D.
INSERM-U955, Institut Henri Mondor
51 Avenue du Maréchal de Lattre de Tassigny
94010 Créteil, France
E-mail: [email protected]
Tel: 33(0)149812123
Potential conflict of interest: Dr. Samuel consults for Astellas, Bristol-Myers Squibb, Gilead, LFB, MSD, Roche, Biotest, AbbVie, and Intercept.
Supported (PAIRINCA CHC, 2009) by the “Agence Nationale Recherche sur le SIDA” (ANRS), the “Institut National du Cancer” (INCA), the “Association pour la Recherche Contre le Cancer” (ARC), and the “Réseau français des biobanques des tumeurs hépatiques.”
Abstract
Hepatitis B virus (HBV) is a major cause of hepatocellular carcinoma (HCC). However, very little is known about the replication of HBV in HCC tissues. We analyzed viral and cellular parameters in HCC (T) and nontumor liver (NT) samples from 99 hepatitis B surface antigen (HBsAg)-positive, virologically suppressed patients treated by tumor resection or liver transplantation. We examined total HBV DNA and RNA as well as covalently closed circular DNA (cccDNA) and pregenomic RNA (pgRNA), which are considered as markers of active HBV replication. Total HBV DNA and RNA were detected in both T and NT samples in a majority of cases, but only a subset of tumors harbored detectable levels of HBV cccDNA and pgRNA (39% and 67%) compared to NT livers (66% and 90%; P < 0.01). Further evidence for HBV replication in tumor tissues was provided by sequencing of the X gene derived from episomal forms, showing that HBV genotypes differed between T and matched NT samples in 11 cases. The detection of pgRNA and cccDNA in tumors was correlated to the absence of tumorous microvascular invasion and to better patient survival. Analysis of gene expression profiles by Agilent microarrays revealed that pgRNA-positive HCCs were characterized by low levels of cell cycle and DNA repair markers and expression of the HBV receptor, sodium taurocholate cotransporting polypeptide, indicating well-differentiated tumors. Conclusion: HCC replicating HBV represents a subtype of weakly invasive HCC with a transcriptomic signature. pgRNA originating from nonintegrated, complete HBV genomes is a sensitive marker for viral replication and prognosis. (Hepatology 2018;67:86-96). 作者: StephenW 时间: 2017-12-21 20:23
乙型肝炎病毒前基因组RNA在肝细胞癌：A Nosological and Prognostic Determinants