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Gene expression profiles of differentiated Huh7.5.1 cells infected with HCV Jc1 clone

ABSTRACT: Hepatocellular carcinoma (HCC) is the second leading cause of cancer death. Curative approaches are limited and chemoprevention is not available. A 186-gene signature in liver tissue predicts HCC risk in cirrhotic patients of various etiologies. However, the drivers of the HCC risk gene signature remain to be fully elucidated. Here, we develop a simple and robust liver cell-based system in which persistent hepatitis B and C virus infection or ethanol exposure induce this signature. We identified candidate drivers of the HCC high-risk signature and hepatocarcinogenesis and uncovered reversal of the signature by an EGFR inhibitor and pioglitazone, a computationally predicted inhibitory compound. This cell-based model unravels the cell circuits of liver disease progression and identifies HCC chemoprevention targets for clinical evaluation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE66842 | GEO | 2021/06/28

REPOSITORIES: GEO

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Project description:Gene-expression profiles of hepatitis C-related, early-stage liver cirrhosis Background & Aims: Liver cirrhosis affects 1%M-bM-^HM-^R2% of population and is the major risk factor of hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the US. Non-invasive methods have been developed to identify patients with asymptomatic, early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients newly diagnosed with cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsies from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. Results: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P=.004), progression to advanced cirrhosis (P<.001), and development of HCC (P=.009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidences of HCC were 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. Conclusions: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent their development of HCC. 216 liver biopsy specimens

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Gene expression profiles of differentiated Huh7.5.1 cells infected with HCV Jc1 clone

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