TY - JOUR
T1 - Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis
AU - Hoshida, Yujin
AU - Villanueva, Augusto
AU - Sangiovanni, Angelo
AU - Sole, Manel
AU - Hur, Chin
AU - Andersson, Karin L.
AU - Chung, Raymond T.
AU - Gould, Joshua
AU - Kojima, Kensuke
AU - Gupta, Supriya
AU - Taylor, Bradley
AU - Crenshaw, Andrew
AU - Gabriel, Stacey
AU - Minguez, Beatriz
AU - Iavarone, Massimo
AU - Friedman, Scott L.
AU - Colombo, Massimo
AU - Llovet, Josep M.
AU - Golub, Todd R.
PY - 2013/5
Y1 - 2013/5
N2 - Background & Aims: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive 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 with newly diagnosed cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up 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 incidence of HCC was 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 the development of HCC.
AB - Background & Aims: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive 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 with newly diagnosed cirrhosis but without HCC. Methods: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up 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 incidence of HCC was 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 the development of HCC.
KW - Early Detection
KW - Liver Cancer Prevention
KW - Screening
KW - Whole Genome Gene Expression Profiling
UR - http://www.scopus.com/inward/record.url?scp=84876474584&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2013.01.021
DO - 10.1053/j.gastro.2013.01.021
M3 - Article
AN - SCOPUS:84876474584
SN - 0016-5085
VL - 144
SP - 1024
EP - 1030
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -