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

Yujin Hoshida, Augusto Villanueva, Angelo Sangiovanni, Manel Sole, Chin Hur, Karin L. Andersson, Raymond T. Chung, Joshua Gould, Kensuke Kojima, Supriya Gupta, Bradley Taylor, Andrew Crenshaw, Stacey Gabriel, Beatriz Minguez, Massimo Iavarone, Scott L. Friedman, Massimo Colombo, Josep M. Llovet, Todd R. Golub

Research output: Contribution to journalArticle

93 Citations (Scopus)

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 <.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.

Original languageEnglish (US)
Pages (from-to)1024-1030
Number of pages7
JournalGastroenterology
Volume144
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

Fingerprint

Hepatitis C
Transcriptome
Hepatocellular Carcinoma
Fibrosis
Genes
Liver
Needle Biopsy
Formaldehyde
Cause of Death
Survival Rate
Biomarkers
Incidence

Keywords

  • Early Detection
  • Liver Cancer Prevention
  • Screening
  • Whole Genome Gene Expression Profiling

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Hoshida, Y., Villanueva, A., Sangiovanni, A., Sole, M., Hur, C., Andersson, K. L., ... Golub, T. R. (2013). Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis. Gastroenterology, 144(5), 1024-1030. https://doi.org/10.1053/j.gastro.2013.01.021

Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis. / Hoshida, Yujin; Villanueva, Augusto; Sangiovanni, Angelo; Sole, Manel; Hur, Chin; Andersson, Karin L.; Chung, Raymond T.; Gould, Joshua; Kojima, Kensuke; Gupta, Supriya; Taylor, Bradley; Crenshaw, Andrew; Gabriel, Stacey; Minguez, Beatriz; Iavarone, Massimo; Friedman, Scott L.; Colombo, Massimo; Llovet, Josep M.; Golub, Todd R.

In: Gastroenterology, Vol. 144, No. 5, 05.2013, p. 1024-1030.

Research output: Contribution to journalArticle

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 2013, 'Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis', Gastroenterology, vol. 144, no. 5, pp. 1024-1030. https://doi.org/10.1053/j.gastro.2013.01.021
Hoshida, Yujin ; Villanueva, Augusto ; Sangiovanni, Angelo ; Sole, Manel ; Hur, Chin ; Andersson, Karin L. ; Chung, Raymond T. ; Gould, Joshua ; Kojima, Kensuke ; Gupta, Supriya ; Taylor, Bradley ; Crenshaw, Andrew ; Gabriel, Stacey ; Minguez, Beatriz ; Iavarone, Massimo ; Friedman, Scott L. ; Colombo, Massimo ; Llovet, Josep M. ; Golub, Todd R. / Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis. In: Gastroenterology. 2013 ; Vol. 144, No. 5. pp. 1024-1030.
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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 <.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.",
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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

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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

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