Expression of Dickkopf-1 and Twist2 in Cervical Squamous Cell Carcinoma and Their Correlation with Vasculogenic Mimicry.

Abstract

Wnt/β-catenin signaling, epithelial-mesenchymal transition (EMT), and vasculogenic mimicry (VM) all exert important effects in tumors. Dickkopf-1 (DKK1) is an antagonist of the Wnt/β-catenin, Twist homolog 2 (Twist2) is a key EMT transcription factor involved in cancer cell migration and invasion, and VM participates in the progression and metastasis of a variety of cancers. However, the correlation of DKK1, Twist2, and VM in cervical squamous cell carcinoma(CSC) is still unclear. This study focuses on correlations among these factors as well as their correlation with clinicopathologic data and survival in CSC. DKK1, Twist2, and VM expressions were immunohistochemically examined in 116 CSC tissues and 37 normal cervical tissues. Furthermore, clinical data were processed. The expression levels of these three factors differed between CSC and normal tissues. VM was observed in CSC, but not in normal cervical tissues. Twist2 expression was high in CSC but low in normal cervical tissues, whereas DKK1 expression had the opposite pattern. Tumor cells with VM had a high expression of Twist2 and low expression of DKK1. In addition, DKK1 expression was negatively correlated with Twist2 expression. Analyzing the relationships of DKK1, Twist2, and VM with the data of patients with CSC revealed that DKK1 expression was negatively correlated with the clinical stage, degree of differentiation, depth of infiltration, and lymph node metastasis of tumors. VM and Twist2 expression were positively correlated with the degree of differentiation, the depth of infiltration, and lymph node metastasis. The positive rate of VM was greater in stage II than in stage I. The patients who expressed VM and Twist2 had a reduced overall survival (OS) when compared with patients not expressing these proteins. However, the patients who expressed DKK1 had an increased OS when compared with patients who did not show any DKK1 expression. Multivariate analysis indicated that the expressions of DKK1, Twist2, and VM were prognostic factors for CSC. VM and the expression of DKK1 and Twist2 can be the potential prognostic biomarkers and therapeutic targets for CSC.