Serum vascular endothelial growth factor A and vascular endothelial growth factor receptor 2 as prognostic biomarkers for uterine cervical cancer.

Abstract

There are few studies on serum vascular endothelial growth factors and receptors (VEGF/VEGFRs) in patients with uterine cervical cancer (CC). The aim of this study was to determine whether VEGF/VEGFRs could be used as prognostic biomarkers in patients with CC. A total of 107 patients with stage IB to IIB CC, who underwent radical hysterectomy at Tottori University Hospital between 2006 and 2015, were included in this study. Serum samples were collected prior to radical hysterectomy, and levels of VEGF-A, VEGF-C, VEGFR-1, and VEGFR-2 were analyzed by enzyme-linked immunosorbent assays. We evaluated the association between the levels of these angiogenic factors and clinicopathologic variables. Survival analysis of 93 patients treated between 2006 and 2013 was performed. The levels of VEGF-A in patients with bulky tumor, pelvic lymph-node involvement (PLNI), and parametrial infiltration (PI) were significantly higher than those in patients without these factors (P = 0.022, P = 0.020, and P = 0.0013, respectively). The overall survival (OS) of patients with high VEGF-A and VEGFR-2 defined by median levels was significantly lower than the OS of patients with low levels of VEGF-A and VEGFR-2 (P = 0.014, P = 0.012, respectively). Multivariate analysis revealed that PLNI, serum VEGF-A levels, and serum VEGFR-2 levels were independent prognostic factors for OS (hazard ratio for VEGF-A 3.42, 95% CI 1.07-13.2; hazard ratio for VEGFR-2 6.37, 95% CI 1.59-43.5). Our results suggest that serum VEGF-A and VEGFR-2 may be promising prognostic biomarkers for CC.