|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Hoshida, Y, Villanueva, A, Sangiovanni, A, Sole, M, Hur, C, Andersson, KL, Chung, RT, Gould, J, Kojima, K, Gupta, S, Taylor, B, Crenshaw, A, Gabriel, S, Minguez, B, Iavarone, M, Friedman, SL, Colombo, M, Llovet, JM, Golub, TR|
BACKGROUND & AIMS:: Liver cirrhosis affects 1%-2% 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 =. ). 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.