title: Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis.
abstract: OBJECTIVE
  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.
authors: Mount Sinai Liver Cancer Program, Tisch Cancer Institute, Division of Liver Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. yujin.hoshida@mssm.edu
authors: Yujin
authors: Y
authors: Hoshida
authors: Augusto
authors: A
authors: Villanueva
authors: Angelo
authors: A
authors: Sangiovanni
authors: Manel
authors: M
authors: Sole
authors: Chin
authors: C
authors: Hur
authors: Karin L
authors: KL
authors: Andersson
authors: Raymond T
authors: RT
authors: Chung
authors: Joshua
authors: J
authors: Gould
authors: Kensuke
authors: K
authors: Kojima
authors: Supriya
authors: S
authors: Gupta
authors: Bradley
authors: B
authors: Taylor
authors: Andrew
authors: A
authors: Crenshaw
authors: Stacey
authors: S
authors: Gabriel
authors: Beatriz
authors: B
authors: Minguez
authors: Massimo
authors: M
authors: Iavarone
authors: Scott L
authors: SL
authors: Friedman
authors: Massimo
authors: M
authors: Colombo
authors: Josep M
authors: JM
authors: Llovet
authors: Todd R
authors: TR
authors: Golub
mesh_terms: D001707:Biopsy, Needle; D004247:DNA / Q000235:genetics*; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D059467:Transcriptome / Q000235:genetics*
chemical_list: D004247:DNA