Tie-2, G-CSF, and Leptin as Promising Diagnostic Biomarkers for Endometrial Cancer: A Pilot Study

Abstract

Preoperative determination of the extent of endometrial cancer (EC) would avoid the complications associated with radical surgery. Screening of patients' plasma biomarkers might enable a more precise diagnosis of EC and a tailored treatment approach. This prospective case-control monocentric pilot study included 76 postmenopausal women (38 endometrioid EC patients and 38 control patients with benign gynecological conditions), and 37 angiogenic factors (AFs) were investigated as potential biomarkers for EC. AF concentrations in preoperative plasma samples were measured using Luminex xMAP™ multiplexing technology. The plasma levels of sTie-2 and G-CSF were significantly lower in EC compared to control patients, whereas the plasma levels of leptin were significantly higher in EC patients. Neuropilin-1 plasma levels were significantly higher in patients with type 2 EC (grade 3) compared to patients with lower grade cancer or controls. Follistatin levels were significantly higher in patients with lymphovascular invasion, and IL-8 plasma levels were significantly higher in patients with metastases. If validated, the plasma concentrations of the indicated AFs could represent an important additional diagnostic tool for the early detection and characterization of EC. This could guide the decision-making on the extent of surgery. Further studies with larger patient numbers are currently ongoing.

Keywords: G-CSF; Tie-2; angiogenesis; angiogenic factors; biomarkers; endometrial cancer; leptin.

Figure 1

The angiogenic factors involved in the pathology of endometrioid EC. Created with BioRender.com.

Figure 2

Box plots (min to max with all points shown) comparing plasma levels of angiogenic biomarkers (pg/mL) between study groups. (A–C) Control and endometrial cancer (EC) patients. (D) Control patients and patients with different grades of EC. (E,F) Control patients and patients with or without lymphovascular invasion (LVI). (G,H) Control patients and patients with or without metastasis (MET). * signifies p < 0.05.

Figure 3

Diagnostic receiver operating characteristic (ROC) curves with area under the curve (AUC) values for three angiogenic biomarkers compared to CA-125 and HE-3.