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The distinct signatures of VEGF and soluble VEGFR2 increase prognostic implication in gastric cancer

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Authors
Ock, Chan-Young; Nam, Ah-Rong; Bang, Ju-Hee; Kim, Tae-Yong; Lee, Kyung-Hun; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Bang, Yung-Jue; Oh, Do-Youn
Issue Date
2015-11
Citation
American Journal of Cancer Research, Vol.5 No.11, pp.3376-3388
Keywords
VEGFsVEGFR2CAFcytokinegastric cancer
Abstract
Recently, an anti-angiogenic strategy to treat gastric cancer (GC) has been successful with the use of ramucirumab. The comprehensive network of VEGF, soluble VEGF receptor-2 (sVEGFR2) and cytokines and other angiogenic factors (CAF) in GC has not been reported. We aimed to reveal the CAF signature associated with VEGF and sVEGFR2, and to explore their prognostic implication in GC. We measured pretreatment serum levels of 52 CAFs, including VEGF and sVEGFR2, using multiplex bead immunoassays and ELISA, in 70 GC patients treated with palliative chemotherapy. Linear regression analysis for correlating CAFs with VEGF and sVEGFR2, and survival analysis were performed. Results from the current analysis showed the VEGF signature was shown to be associated with seven CAFs (IL-7, IL-12p70, IL-2Ra, IL-10, stem cell factor, FGF2b, IL-3). The sVEGFR2 signature was associated with IL-4 and PDGFb. VEGF and sVEGFR2 showed no association with each other. High VEGF was associated with worse OS (11.2 months, high-VEGF versus 16.7 months, low-VEGF; P = 0.061). However, among patients with high-sVEGFR2, OS was not different according to VEGF (12.1 months, high-VEGF versus 15.1 months, low-VEGF; P = 0.546). In patients with low-sVEGFR2, OS was significantly different according VEGF (10.9 months, high-VEGF versus 16.8 months, low-VEGF, P = 0.036). In multivariate analysis, a high VEGF/sVEGFR2 ratio was significantly correlated with worse OS (HR 1.78 [95% CI 1.08-2.94], P = 0.024). In conclusion, VEGF and sVEGFR2 had distinct CAF signatures in GC. Consideration of both VEGF and sVEGFR2 confers more accurate prognostic implication compared with VEGF alone in GC.
ISSN
2156-6976
URI
https://hdl.handle.net/10371/172943
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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