A hepatic stellate cell gene expression signature associated with outcomes in hepatitis C cirrhosis and hepatocellular carcinoma after curative resection.
- Zhang DY Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
- Goossens N 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.
- Guo J 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.
- Tsai MC 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.
- Chou HI Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
- Altunkaynak C Department of Medicine, Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
- Sangiovanni A 1st Division of Gastroenterology, M. & A. Migliavacca Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
- Iavarone M 1st Division of Gastroenterology, M. & A. Migliavacca Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
- Colombo M 1st Division of Gastroenterology, M. & A. Migliavacca Center for Liver Disease, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Milan, Italy.
- Kobayashi M Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
- Kumada H Department of Hepatology, Toranomon Hospital, Tokyo, Japan.
- Villanueva A 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.
- Llovet JM 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.
- Hoshida Y 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.
- Friedman SL 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.
- 2015-06-06
Published in:
- Gut. - 2016
HEPATIC FIBROSIS
HEPATIC STELLATE CELL
LIVER CIRRHOSIS
LIVER FAILURE
Animals
Carcinoma, Hepatocellular
Disease Progression
Extracellular Matrix Proteins
Gene Expression Profiling
Hepatic Stellate Cells
Hepatitis C
Humans
Liver Cirrhosis
Liver Neoplasms
Mice
Prognosis
Rats
Recurrence
Risk Assessment
Transcriptome
English
OBJECTIVE
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.
DESIGN
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.
RESULTS
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.
CONCLUSIONS
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.
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.
DESIGN
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.
RESULTS
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.
CONCLUSIONS
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.
- Language
-
- English
- Open access status
- green
- Identifiers
-
- DOI 10.1136/gutjnl-2015-309655
- PMID 26045137
- Persistent URL
- https://sonar.ch/global/documents/246016
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