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Gastroenterology DOI:10.1053/j.gastro.2013.01.021

Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis.

Publication TypeJournal Article
Year of Publication2013
AuthorsHoshida, 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
JournalGastroenterology
Volume144
Issue5
Pages1024-30
Date Published2013 May
ISSN1528-0012
KeywordsBiopsy, Needle, Disease Progression, DNA, Early Diagnosis, Female, Follow-Up Studies, Gene Expression Regulation, Genetic Predisposition to Disease, Hepatitis C, Chronic, Humans, Liver, Liver Cirrhosis, Male, Middle Aged, Prognosis, Time Factors, Transcriptome
Abstract

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

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.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0016-5085(13)00078-4
DOI10.1053/j.gastro.2013.01.021
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/23333348?dopt=Abstract

Alternate JournalGastroenterology
PubMed ID23333348
PubMed Central IDPMC3633736
Grant ListR01 DK056621 / DK / NIDDK NIH HHS / United States
1R01DK076986-01 / DK / NIDDK NIH HHS / United States
K24 DK078772 / DK / NIDDK NIH HHS / United States
P30 DK043351 / DK / NIDDK NIH HHS / United States
R01 DK076986 / DK / NIDDK NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
R01 DK098079 / DK / NIDDK NIH HHS / United States
AA017067 / AA / NIAAA NIH HHS / United States
P20 AA017067 / AA / NIAAA NIH HHS / United States
AI069939 / AI / NIAID NIH HHS / United States
U54 CA112962 / CA / NCI NIH HHS / United States
R01 DK037340 / DK / NIDDK NIH HHS / United States
DK078772 / DK / NIDDK NIH HHS / United States
R01 DK056601 / DK / NIDDK NIH HHS / United States
R01 AI069939 / AI / NIAID NIH HHS / United States