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.
Gene-expression signature of vascular invasion in hepatocellular carcinoma / B. Mínguez, Y. Hoshida, A. Villanueva, S. Toffanin, L. Cabellos, S. Thung, J. Mandeli, D. Sia, C. April, J. Fan, A. Lachenmayer, R. Savic, S. Roayaie, V. Mazzaferro, J. Bruix, M. Schwartz, S.L. Friedman, J.M. Llovet. - In: JOURNAL OF HEPATOLOGY. - ISSN 0168-8278. - 55:6(2011), pp. 1325-1331.
|Titolo:||Gene-expression signature of vascular invasion in hepatocellular carcinoma|
|Parole Chiave:||Hepatocellular carcinoma; Vascular invasion; Gene-expression signature; Surgical resection; Liver transplantation; Prediction; Diagnosis|
|Settore Scientifico Disciplinare:||Settore MED/18 - Chirurgia Generale|
|Data di pubblicazione:||2011|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.jhep.2011.02.034|
|Appare nelle tipologie:||01 - Articolo su periodico|