Circulating Tie2-Expressing Monocytes: A Potential Biomarker for Cervical Cancer

Background: Tyrosine kinase with immunoglobulin and epidermal growth factor homology domains 2 (Tie2)-expressing monocytes (TEMs) are a highly proangiogenic subset of myeloid cells, which are characterized by expressing the angiopoietin receptor Tie2 with pro-tumor activity.

Purpose: The present study aimed to determine the clinical value of circulating TEMs (cTEMs) for cervical cancer.

Patients and methods: Peripheral blood mononuclear cells (PBMCs) were obtained from 7 healthy volunteers, 17 uterine fibroid patients, 24 cervical intraepithelial neoplasia (CIN) II patients, 31 CIN III patients and 99 patients with cervical cancer. The cTEMs were evaluated by the ratio of Tie2⁺ CD14⁺ cells to all CD14⁺ monocytes in the PBMCs through flow cytometry. The diagnostic value of cTEM was assessed by receiver operating characteristic (ROC) curves and the correlation between cTEM and clinicopathological characters in cervical cancer patients was analyzed.

Results: The proportion of cTEMs was gradually increasing from healthy volunteers to patients with non-invasive lesions, then to cervical cancer patients. The area under the ROC curve was 0.913 when the level of cTEMs was used to distinguish cervical cancer from all the other women ranging from healthy volunteers to CIN III patients. In cervical cancer, an increased cTEM fraction was significantly correlated with advanced tumor stage, larger tumor size, lymph node metastasis (LNM), deep stromal infiltration, parametrial involvement and lymph-vascular space invasion and was an independent risk factor for LNM.

Conclusion: The cTEM proportion might be a promising biomarker for the malignant transformation of cervical lesions and the progression of cervical cancer.

Keywords: Tie2-expressing monocytes; biomarker; cervical cancer; lymph node metastasis; tumor associated macrophages; tumor progression.