Gene-expression signature of vascular invasion in hepatocellular carcinoma

Beatriz Mínguez, Yujin Hoshida, Augusto Villanueva, Sara Toffanin, Laia Cabellos, Swan Thung, John Mandeli, Daniela Sia, Craig April, Jian Bing Fan, Anja Lachenmayer, Radoslav Savic, Sasan Roayaie, Vincenzo Mazzaferro, Jordi Bruix, Myron Schwartz, Scott L. Friedman, Josep M. Llovet

Research output: Contribution to journalArticle

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Abstract

Background & Aims: Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30-40% of patients with early tumors, remains elusive. Methods: A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. Results: A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48-7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17-6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). Conclusions: The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.

Original languageEnglish (US)
Pages (from-to)1325-1331
Number of pages7
JournalJournal of Hepatology
Volume55
Issue number6
DOIs
StatePublished - Dec 1 2011
Externally publishedYes

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Transcriptome
Blood Vessels
Hepatocellular Carcinoma
Neoplasms
Investigational Therapies
Gene Expression Profiling
Hepatitis C
Liver Transplantation
Paraffin
Formaldehyde
Clinical Trials
Genome
Recurrence
Genes

Keywords

  • Diagnosis
  • Gene-expression signature
  • Hepatocellular carcinoma
  • Liver transplantation
  • Prediction
  • Surgical resection
  • Vascular invasion

ASJC Scopus subject areas

  • Hepatology

Cite this

Mínguez, B., Hoshida, Y., Villanueva, A., Toffanin, S., Cabellos, L., Thung, S., ... Llovet, J. M. (2011). Gene-expression signature of vascular invasion in hepatocellular carcinoma. Journal of Hepatology, 55(6), 1325-1331. https://doi.org/10.1016/j.jhep.2011.02.034

Gene-expression signature of vascular invasion in hepatocellular carcinoma. / Mínguez, Beatriz; Hoshida, Yujin; Villanueva, Augusto; Toffanin, Sara; Cabellos, Laia; Thung, Swan; Mandeli, John; Sia, Daniela; April, Craig; Fan, Jian Bing; Lachenmayer, Anja; Savic, Radoslav; Roayaie, Sasan; Mazzaferro, Vincenzo; Bruix, Jordi; Schwartz, Myron; Friedman, Scott L.; Llovet, Josep M.

In: Journal of Hepatology, Vol. 55, No. 6, 01.12.2011, p. 1325-1331.

Research output: Contribution to journalArticle

Mínguez, B, Hoshida, Y, Villanueva, A, Toffanin, S, Cabellos, L, Thung, S, Mandeli, J, Sia, D, April, C, Fan, JB, Lachenmayer, A, Savic, R, Roayaie, S, Mazzaferro, V, Bruix, J, Schwartz, M, Friedman, SL & Llovet, JM 2011, 'Gene-expression signature of vascular invasion in hepatocellular carcinoma', Journal of Hepatology, vol. 55, no. 6, pp. 1325-1331. https://doi.org/10.1016/j.jhep.2011.02.034
Mínguez, Beatriz ; Hoshida, Yujin ; Villanueva, Augusto ; Toffanin, Sara ; Cabellos, Laia ; Thung, Swan ; Mandeli, John ; Sia, Daniela ; April, Craig ; Fan, Jian Bing ; Lachenmayer, Anja ; Savic, Radoslav ; Roayaie, Sasan ; Mazzaferro, Vincenzo ; Bruix, Jordi ; Schwartz, Myron ; Friedman, Scott L. ; Llovet, Josep M. / Gene-expression signature of vascular invasion in hepatocellular carcinoma. In: Journal of Hepatology. 2011 ; Vol. 55, No. 6. pp. 1325-1331.
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abstract = "Background & Aims: Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30-40{\%} of patients with early tumors, remains elusive. Methods: A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. Results: A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69{\%}. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95{\%} CI 1.48-7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95{\%} CI 1.17-6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). Conclusions: The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.",
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T1 - Gene-expression signature of vascular invasion in hepatocellular carcinoma

AU - Mínguez, Beatriz

AU - Hoshida, Yujin

AU - Villanueva, Augusto

AU - Toffanin, Sara

AU - Cabellos, Laia

AU - Thung, Swan

AU - Mandeli, John

AU - Sia, Daniela

AU - April, Craig

AU - Fan, Jian Bing

AU - Lachenmayer, Anja

AU - Savic, Radoslav

AU - Roayaie, Sasan

AU - Mazzaferro, Vincenzo

AU - Bruix, Jordi

AU - Schwartz, Myron

AU - Friedman, Scott L.

AU - Llovet, Josep M.

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Background & Aims: Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30-40% of patients with early tumors, remains elusive. Methods: A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. Results: A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48-7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17-6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). Conclusions: The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.

AB - Background & Aims: Vascular invasion is a major predictor of tumor recurrence after surgical treatments for hepatocellular carcinoma (HCC). While macroscopic vascular invasion can be detected by radiological techniques, pre-operative detection of microscopic vascular invasion, which complicates 30-40% of patients with early tumors, remains elusive. Methods: A total of 214 patients with hepatocellular carcinoma who underwent resection were included in the study. By using genome-wide gene-expression profiling of 79 hepatitis C-related hepatocellular carcinoma samples (training set), a gene-expression signature associated with vascular invasion was defined. The signature was validated in formalin-fixed paraffin-embedded tissues obtained from an independent set of 135 patients with various etiologies. Results: A 35-gene signature of vascular invasion was defined in the training set, predicting vascular invasion with an accuracy of 69%. The signature was independently associated with the presence of vascular invasion (OR 3.38, 95% CI 1.48-7.71, p = 0.003) along with tumor size (diameter greater than 3 cm, OR 2.66, 95% CI 1.17-6.05, p = 0.02). In the validation set, the signature discarded the presence of vascular invasion with a negative predictive value of 0.77, and significantly improved the diagnostic power of tumor size alone (p = 0.045). Conclusions: The assessment of a gene-expression signature obtained from resected biopsied tumor specimens improved the diagnosis of vascular invasion beyond clinical variable-based prediction. The signature may aid in candidate selection for liver transplantation, and guide the design of clinical trials with experimental adjuvant therapies.

KW - Diagnosis

KW - Gene-expression signature

KW - Hepatocellular carcinoma

KW - Liver transplantation

KW - Prediction

KW - Surgical resection

KW - Vascular invasion

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