Abstract
ObjectivesAngiopoietins have been found to play essential roles in tumor angiogenesis. The present study was aimed at investigating the diagnostic and prognostic values of serum angiopoietin 1 and 2 (sAng-1 and sAng-2) in cervical cancer.MethodsThe sAng-1 and sAng-2 concentrations were analyzed in 77 women with cervical cancer, 44 women with cervical intraepithelial neoplasia (CIN) and 43 women without cervical lesions by enzyme-linked immunosorbent assay. The diagnostic values of sAng-1, sAng-2 and sAng-1/sAng-2 were evaluated by receiver operating characteristic (ROC) curves. The Ang-1 and Ang-2 expression in cervical cancer tissues as well as microvessel density (MVD), were assessed by immunohistochemistry.ResultsThe concentration of sAng-2 gradually increased and the sAng-1/Ang-2 ratio was gradually decreased from normal control to CIN, then to squamous cell cancer, and the sAng-1/sAng-2 ratio was also significantly decreased in adenocarcinoma. The area under ROC curves of sAng-2 and sAng-1/sAng-2 ratio for discriminating cervical cancer from normal were 0.744 and 0.705, respectively. Decreased sAng-1/sAng-2 was significantly associated with advanced tumor stage, poor differentiation, lymph-vascular space invasion and high MVD. sAng-2 was positively correlated with the Ang-2 expression in cervix epithelia. A high sAng-1/sAng-2 ratio was associated with a longer progression-free survival and a longer overall survival in cervical cancer patients.ConclusionsThese findings suggest that sAng-2 and the sAng-1/sAng-2 ratio may be valuable diagnostic and prognostic biomarkers for cervical cancer.
Highlights
Cervical cancer incidence has increased from 378,000 cases per year in 1980 to 528,000 cases per year in 2012, representing a 0.6% annual rate of increase (Ferlay et al, 2015)
We found that the concentration of serum Ang-2 (sAng-2) was significantly increased in patients with cervical cancer compared with normal controls and cervical intraepithelial neoplasia (CIN) patients and the sAng-1/sAng-2 ratio was decreasing during the malignant transformation of cervical epithelia
In patients with cervical cancer, low sAng-1/sAng-2 ratio was significantly associated with advanced stage, poor differentiation, lymphovascular space invasion (LVSI), high microvessel density (MVD) and poor survival
Summary
Cervical cancer incidence has increased from 378,000 cases per year in 1980 to 528,000 cases per year in 2012, representing a 0.6% annual rate of increase (Ferlay et al, 2015). Angiopoietins have been shown to directly interact with integrins on endothelial, mesenchymal and tumor cells, thereby eliciting Tie-2-independent biological effects (Augustin et al, 2009; Fagiani & Christofori, 2013; Shim, Ho & Wong, 2007) Both Ang-1 and -2 have recently been found to be expressed in tumor cells, and they act cooperatively with VEGF promoting the angiogenesis during tumor progression (Augustin et al, 2009; Ebos & Kerbel, 2011; Gerald et al, 2013; Shim, Ho & Wong, 2007; Yang et al, 2015)
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