Gene-expression signature of vascular invasion in hepatocellular carcinoma

J Hepatol. 2011 Dec;55(6):1325-31. doi: 10.1016/j.jhep.2011.02.034. Epub 2011 Apr 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / blood supply*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / surgery
  • Female
  • Gene Expression Profiling
  • Humans
  • Liver Neoplasms / blood supply*
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Liver Neoplasms / surgery
  • Liver Transplantation
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • Risk Factors