Abstract 5735: Comprehensive analysis of serum levels of VEGF and its receptors in patients with uterine cervical cancer
Authors: Osaku Daiken , Oishi Tetsuro , Sawada Mayumi , Komatsu Hiroaki , Chikumi Jun , Kudoh Akiko , Nonaka Michiko , Sato Shinya , Shimada Muneaki , Itamochi Hiroaki , Harada Tasuku 
Published: July 2017

Abstract
Objective: Angiogenesis is one of the processes that is critical for the growth, invasion and metastasis of solid tumors, including uterine cervical cancer (CC). The vascular endothelial growth factor (VEGF) family is one of the major pathways involved in tumor angiogenesis. The aim of this study was to determine whether serum levels of these angiogenic factors could be used as biomarkers in patients with CC.Methods: A total of 107 patients with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IIB CC who were treated at Tottori University Hospital between 2006 and 2015 were enrolled in this study. The study was approved by the Institutional Review Board of the School of Medicine of Tottori University. All patients gave written informed consent before the collection of specimens according to institutional guidelines. Serum samples were collected before initial surgery and levels of VEGF-A, -C, VEGFR-1, and VEGFR-2 were analyzed by enzyme-linked immunosorbent assay (ELISA). We evaluated the association between the levels of these angiogenic factors and clinicopathologic variables. With a median follow-up duration of 1743 days, survival analysis of 93 patients treated between 2006 and 2013 was performed. We also determined the mRNA expression of VEGF-A by real-time RT-PCR in fresh frozen tumors and the protein expression by immunohistochemical staining in paraffin-embedded tumors from CC patients. The mRNA levels of VEGF-A relative to GAPDH were used for the analysis.Results: Median levels of serum VEGF-A, -C, VEGFR-1, and VEGFR-2 were 313, 8122, 68, and 6210 pg/ml, respectively. We found a significant positive correlation between VEGF-A levels and the maximum tumor diameter (P=0.010). Patients with pelvic lymph node involvement (PLNI) showed significantly higher levels of VEGF-A and VEGFR-2 than those without PLNI. Patients with bulky tumor or parametrial infiltration (PI) also showed significantly higher levels of VEGF-A. In contrast, patients with a bulky tumor or PLNI showed significantly lower levels of VEGFR-1. Both histological types and FIGO stage were not related to levels of these angiogenic factors. We set the cutoff values of these factors at the median levels of the angiogenic factors. The 5-year overall survival rate (OS) for patients with high VEGF-A levels was significantly lower than those with low levels (92.9% vs. 72.8%, P = 0.014). The 5-year OS for patients with high VEGFR-2 levels was significantly lower than those with low levels (94.7% vs. 73.8%, P = 0.012). PLNI and PI were prognostic factors for overall survival. Multivariate analysis revealed that PLNI, VEGF-A, and VEGFR-2 levels were independent prognostic factors. The mRNA and protein expressions of VEGF-A were strongly observed in the cancer cells. There was no correlation between mRNA levels and serum levels of VEGF-A.Conclusion: These results suggest that serum VEGF-A may be a promising prognostic biomarker for CC.
Citation Format: Daiken Osaku, Tetsuro Oishi, Mayumi Sawada, Hiroaki Komatsu, Jun Chikumi, Akiko Kudoh, Michiko Nonaka, Shinya Sato, Muneaki Shimada, Hiroaki Itamochi, Tasuku Harada. Comprehensive analysis of serum levels of VEGF and its receptors in patients with uterine cervical cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5735. doi:10.1158/1538-7445.AM2017-5735