A VEGF-dependent gene signature enriched in mesenchymal ovarian cancer predicts patient prognosis

Abstract

We have previously reported surrogate biomarkers of VEGF pathway activities with the potential to provide predictive information for anti-VEGF therapies. The aim of this study was to systematically evaluate a new VEGF-dependent gene signature (VDGs) in relation to molecular subtypes of ovarian cancer and patient prognosis. Using microarray profiling and cross-species analysis, we identified 140-gene mouse VDGs and corresponding 139-gene human VDGs, which displayed enrichment of vasculature and basement membrane genes. In patients who received bevacizumab therapy and showed partial response, the expressions of VDGs (summarized to yield VDGs scores) were markedly decreased in post-treatment biopsies compared with pre-treatment baselines. In contrast, VDGs scores were not significantly altered following bevacizumab treatment in patients with stable or progressive disease. Analysis of VDGs in ovarian cancer showed that VDGs as a prognostic signature was able to predict patient outcome. Correlation estimation of VDGs scores and molecular features revealed that VDGs was overrepresented in mesenchymal subtype and BRCA mutation carriers. These findings highlighted the prognostic role of VEGF-mediated angiogenesis in ovarian cancer, and proposed a VEGF-dependent gene signature as a molecular basis for developing novel diagnostic strategies to aid patient selection for VEGF-targeted agents.

The Prognostic 97 Chemoresponse Gene Signature in Ovarian Cancer

“…Moreover, we investigated transcription factors included in the 97-gene signature. Consistent with previous studies, p53 35 , 36 and HIF1α 22 were the upregulated transcription factors. However, a previous study reported that a large phase III trial of adenoviral wild-type p53 delivery combined with taxol and carboplatinum did not show any positive results in ovarian cancer 37 .…”

Recommendations for biomarker testing in epithelial ovarian cancer: a National Consensus Statement by the Spanish Society of Pathology and the Spanish Society of Medical Oncology

“…As regards tumour VEGF levels, the only evidence was that elevated VEGF levels (tVEGF) had a negative impact on patient survival at early stages [71]. More recent genomic signature studies, including multiple genes related to this pathway, confirm the adverse prognostic value of elevated VEGF expression levels [72].…”

FSH receptor binding inhibitor impacts K-Ras and c-Myc of ovarian cancer and signal pathway

“…The overexpression of c-Myc proteins probably promotes the process of malignant change and progression of tumor [ 20 , 21 ]. Therefore, the Myc family is an excellent target for anti-cancer therapeutics [ 22 , 23 ].…”

“…Angiogenesis is a crucial feature of EOC pathogenesis [ 22 ]. Vascular endothelial growth factor (VEGF) is the most important angiogenesis promoter [ 23 , 24 ]. VEGF protein has been consistently associated with EOC progression [ 23 , 25 ].…”