P.08.18 THE ROLE OF VEGF AND VEGFR POLYMORPHISMS IN THE PREDICTION OF CLINICAL OUTCOME FOR ADVANCED HEPATOCELLULAR CARCINOMA RECEIVING SORAFENIB

Abstract

Background and aim: Hepatocellular carcinoma (HCC) still represents a medical challenge in cancer therapy. In recent years the introduction of new targeted therapies has radically changed the approach to the disease and patients outcome. Currently the therapeutic stronghold is a TKIs directed against the VEGF family (sorafenib). Polymorphisms of VEGF and its receptor genes are involved in regulating angiogenesis and lymphangiogenesis and thus in growth tumor control. We week to evaluate the potential predictive and prognostic role of VEGF and VEGFR polymorphisms in determining the clinical outcome of HCC patients receiving sorafenib. Material and methods:17 histologic samples (biopsies and surgical specimens) of HCC patients receiving sorafenib were tested for VEGF-A, VEGF-C and VEGFR-1,2,3 single nucleotide polymorphisms (SNPs). Patients time to progression (TTP) and overall survival (OS) were analysed. Results: VEGF-AI rs25648 C>T polymorphism was statistically significant in OS (15.0 months for C vs9.4 months for T; p=0.025). VEGF-AII rs10434 G>A was statistically significant for TTP (4.1 months for G vs1.2 months for A; p=0.0076) and OS (14.2 months for G vs1.7 for A; p<0.0001). VEGF-CII rs7664413 C>T was significant in TTP (13.4 months for C vs2.0 for T; p=0.0125) and OS (14.7 months for C vs 5.6 for T; p=0.0007). VEGR2-I rs1870377 A>T was significant in TTP (19.9 months for A vs 3.0 for T; p=0.0271) and OS (29.6 months for A vs11.9 for T; p=0.0096). Conclusions: In our analysis patients with G polymorphism at rs10434, C polymorphism at rs7664413 and A polymorphism at rs1870377 have a better response (PFS and OS) during treatment with sorafenib. Patients with C polymorphism of rs7664413 and A polymorphism of rs1870377 show a favourable impact in this setting. Notably, VEGFr polymorphism results closely related to the treatment response and the specific signalling of sorafenib. Thus analysis of VEGF and its receptor genes polymorphisms may represents a clinical tool to identify patients with a favourable response to sorafenib treatment presumably related to a more efficient control of tumor growth.