VEGI downregulation is correlated with nodal metastasis and poor prognosis in lung adenocarcinoma.

Abstract

Although the incidence of lung cancer is increasing worldwide, the molecular mechanisms for its tumorigenesis, progression and prognosis remain unknown. As a member of the tumor necrosis factor superfamily, vascular endothelial growth inhibitor (VEGI) is involved in the development and progression of many malignant diseases. In the present study, the expression of VEGI and CD31 was examined via immunohistochemistry in non-small cell lung cancer (NSCLC) tissues obtained from 150 patients with NSCLC. The inhibitory effect of VEGI on tumor-associated blood vessel formation and growth was investigated by determining the relationship between VEGI protein expression and microvascular density (MVD). Prognostic significance was evaluated using the Kaplan-Meier method. VEGI expression was downregulated or lost in 68.7% (103/150) of patients with NSCLC, an effect that was more prevalent in adenocarcinoma (AC), 76.0% (57/75), than in squamous cell carcinoma, 61.3% (46/75). A significant negative correlation was indentified between VEGI expression and lymphovascular invasion (P=0.039) and lymph node metastasis (P=0.017) in AC tissue. Additionally, MVD was significantly lower in the VEGI-rich group compared with the VEGI-poor group. The downregulation of VEGI expression was also associated with poorer overall survival (P=0.011) in patients with AC. The present study therefore provides evidence that VEGI may be a new and effective prognostic marker of lung AC.