Expression of endothelial nitric oxide synthase correlates with the angiogenic phenotypes and poor prognosis of human gastric cancer / 肿瘤

ABSTRACT

Objective: Angiogenesis is a critical step in tumor growth and is regulated by multiple molecular pathways. We evaluted the expression of nitric oxide synthase (NOS) III and its relationship with the angiogenic phenotypes and expressions of the transcription factor Sp1, as well as their effect on survival rate of patients with gastric cancer. Methods: The expression levels of NOS III and Sp1, and tumor microvessel density (MVD) status in 86 specimens of resected gastric cancer tissues were determined by immunohistochemistry. Results: NOS III protein expression was significantly higher in both primary tumors and lymph node metastases than in normal gastric mucosa. In primary tumors, NOS III expression had close correlation with Sp1 expression (P=0.001) and MVD status (P=0.001). Patients with positive Sp1 expression were more likely to have strong NOS III expression (15 times) and a high MVD (7 times) than those with negative Sp1 expression. Univariate survival analysis showed that strong NOS III expression, strong Sp1 expression, and a high MVD were associated with poor prognosis. In a Cox proportional hazards model, only strong NOS III and Sp1 expression as well as advanced disease stage were independent factors for prognosis of patients. Conclusion: Our results indicate that the expression of NOS III may play an important role in tumor angiogenesis and infiltration of gastric cancer.