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.
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.
Authors: Jian-Bing Fan; Joanne M Yeakley; Marina Bibikova; Eugene Chudin; Eliza Wickham; Jing Chen; Dennis Doucet; Philippe Rigault; Baohong Zhang; Richard Shen; Celeste McBride; Hai-Ri Li; Xiang-Dong Fu; Arnold Oliphant; David L Barker; Mark S Chee Journal: Genome Res Date: 2004-05 Impact factor: 9.043
Authors: F Y Yao; L Ferrell; N M Bass; J J Watson; P Bacchetti; A Venook; N L Ascher; J P Roberts Journal: Hepatology Date: 2001-06 Impact factor: 17.425
Authors: S Jonas; W O Bechstein; T Steinmüller; M Herrmann; C Radke; T Berg; U Settmacher; P Neuhaus Journal: Hepatology Date: 2001-05 Impact factor: 17.425
Authors: Lei Xu; Steven S Shen; Yujin Hoshida; Aravind Subramanian; Ken Ross; Jean-Philippe Brunet; Stephan N Wagner; Sridhar Ramaswamy; Jill P Mesirov; Richard O Hynes Journal: Mol Cancer Res Date: 2008-05 Impact factor: 5.852
Authors: V Mazzaferro; E Regalia; R Doci; S Andreola; A Pulvirenti; F Bozzetti; F Montalto; M Ammatuna; A Morabito; L Gennari Journal: N Engl J Med Date: 1996-03-14 Impact factor: 176.079
Authors: Ingrid Hodorová; Silvia Rybárová; Peter Solár; Marián Benický; Dušan Rybár; Zuzana Kováčová; Jozef Mihalik Journal: Med Sci Monit Date: 2018-08-04