title: A hepatic stellate cell gene expression signature associated with outcomes in hepatitis C cirrhosis and hepatocellular carcinoma after curative resection.
abstract: We used an informatics approach to identify and validate genes whose expression is unique to hepatic stellate cells and assessed the prognostic capability of their expression in cirrhosis.
  
  
  
  We defined a hepatic stellate cell gene signature by comparing stellate, immune and hepatic transcriptome profiles. We then created a prognostic index using a combination of hepatic stellate cell signature expression and clinical variables. This signature was derived in a retrospective-prospective cohort of hepatitis C-related early-stage cirrhosis (prognostic index derivation set) and validated in an independent retrospective cohort of patients with postresection hepatocellular carcinoma (HCC). We then examined the association between hepatic stellate cell signature expression and decompensation, HCC development, progression of Child-Pugh class and survival.
  
  
  
  The 122-gene hepatic stellate cell signature consists of genes encoding extracellular matrix proteins and developmental factors and correlates with the extent of fibrosis in human, mouse and rat datasets. Importantly, association of clinical prognostic variables with overall survival was improved by adding the signature; we used these results to define a prognostic index in the derivation set. In the validation set, the same prognostic index was associated with overall survival. The prognostic index was associated with decompensation, HCC and progression of Child-Pugh class in the derivation set, and HCC recurrence in the validation set.
  
  
  
  This work highlights the unique transcriptional niche of stellate cells, and identifies potential stellate cell targets for tracking, targeting and isolation. Hepatic stellate cell signature expression may identify patients with HCV cirrhosis or postresection HCC with poor prognosis.
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Zhang
authors.affiliation: Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA Division of Gastroenterology and Hepatology, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Goossens
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA Division of Digestive Diseases, Zhongshang Hospital and Fudan University, Shanghai, China.
authors.forename: Jinsheng
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Tsai
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Chou
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Civan
authors.initials: C
authors.lastname: Altunkaynak
authors.affiliation: 1st Division of Gastroenterology, M. & A. Migliavacca Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sangiovanni
authors.affiliation: 1st Division of Gastroenterology, M. & A. Migliavacca Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Iavarone
authors.affiliation: 1st Division of Gastroenterology, M. & A. Migliavacca Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
authors.forename: Massomo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Kumada
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Augusto
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA Liver Cancer Translational Research Lab, Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, Hospital Clínic Barcelona, IDIBAPS, Centro de Investigaciones en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), University of Barcelona, Barcelona, Spain Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.
authors.forename: Josep M
authors.initials: JM
authors.lastname: Llovet
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Yujin
authors.initials: Y
authors.lastname: Hoshida
authors.affiliation: Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA Liver Cancer Program, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Scott L
authors.initials: SL
authors.lastname: Friedman
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000473:pathology / Q000628:therapy; D018450:Disease Progression; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D055166:Hepatic Stellate Cells / Q000502:physiology*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000209:etiology / Q000473:pathology; D008113:Liver Neoplasms / Q000175:diagnosis / Q000209:etiology / Q000473:pathology / Q000628:therapy; D051379:Mice; D011379:Prognosis; D051381:Rats; D012008:Recurrence; D018570:Risk Assessment / Q000379:methods; D059467:Transcriptome / Q000502:physiology*
chemical_list: D016326:Extracellular Matrix Proteins
keywords: HEPATIC FIBROSIS; HEPATIC STELLATE CELL; LIVER CIRRHOSIS; LIVER FAILURE