737P - Angiogenesis polymorphisms profile in the prediction of clinical outcome of advanced HCC patients receiving sorafenib: combined analysis of VEGF an...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Hepatobiliary Cancers
Translational Research
Presenter Luca Faloppi
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors L. Faloppi1, M. Scartozzi1, M. D'Anzeo2, M. Bianconi1, G. Svegliati Baroni3, N. Silvestris4, A. Casadei Gardini5, G. Masi6, R. Giampieri1, M. Del Prete1, A. Benedetti3, S. Cascinu1
  • 1Clinica Di Oncologia Medica, AOU Ospedali Riuniti Ancona Università Politecnica delle Marche, 60126 - Ancona/IT
  • 2Clinica Di Oncologia Medica, UNIVPM, 60126 - Ancona/IT
  • 3Clinica Di Gastroenterologia, UNIVPM, Ancona/IT
  • 4Medical Oncology Unit, National Cancer Institute "Giovanni Paolo II", 70124 - bari/IT
  • 5Medical Oncology, IRCCS Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.), 47014 - Meldola/IT
  • 6Oncologia Medica Universitaria, Azienda Ospedaliero-Universitaria Pisana, 56100 - Pisa/IT

Abstract

Aim

Tumour cells adapt to hypoxic microenvironment via the activation of numerous molecules, among which hypoxia inducible factor 1 (HIF-1) is the most important. HIF-1 plays a crucial role in tumour angiogenesis triggering the transcription of several genes including the vascular endothelial growth factor (VEGF). Currently the therapeutic stronghold of advanced hepatocellular carcinoma (HCC) is the antiangiogenetic TKIs sorafenib. The overexpression of HIF-1 in HCC is significantly associated with tumour angiogenesis, invasion and metastasis, treatment resistance and poor prognosis. In our previous report polymorphisms (SNPs) CC + CG > GG of rs2010963 and TT + CT > CC rs4604006 of VEGF have been shown to predict clinical outcome in HCC patients treated with sorafenib.

Methods

From a large database a preliminary analysis on 90 HCC patients receiving sorafenib was conducted to assess the potential predictive and prognostic role of HIF-1 SNPs in determining the clinical outcome in this setting. Tumour histologic samples were tested for 8 different HIF-1 SNPs. Patients progression free survival (PFS) and overall survival (OS) were analysed.

Results

At univariate analysis CC > AA + AC of rs1951795, TT > CC + CT of rs10873142, AA + AG > GG of rs12434438 SNPs were statistically significant for PFS and OS (Table 1). At multivariate analysis rs1951795 of HIF-1, rs2010963 of VEGF-A and rs4604006 of VEGF-C have been confirmed as independent factors.

HIF-1 SNPs PFS OS
rs1951795 0.0271 0.0174
CC 6.8 16.1
AA + AC 3.0 12.6
rs10873142 0.0427 0.0247
TT 6.7 16.0
CC + TT 3.4 12.7
rs12434438 0.0181 0.0225
AA + AG 6.1 14.7
GG 2.6 10.6

Conclusions

This investigation on HIF-1 SNPs, following our previous discoveries on VEGF and its receptors, may represent a clinical tool to identify patients with favourable response to sorafenib, presumably related to a more efficient control of tumour growth.

Disclosure

All authors have declared no conflicts of interest.