内皮一氧化氮合酶表达与人胃癌血管生成表型及不良预后的相关性研究

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

目的:研究一氧化氮合酶Ⅲ(nitric oxide synthaseⅢ,NOSⅢ)与血管生成表型、转录因子Sp1表达的关系,以及它对胃癌患者生存率的影响。方法:选取86个胃癌病例组织样本,利用免疫组化方法检测组织中NOSⅢ、Sp1以及肿瘤微血管密度(MVD)表达水平。结果:在原发肿瘤及转移淋巴结中,NOSⅢ的表达远远高于其在正常胃黏膜中的表达。在原发肿瘤中,NOSⅢ表达与Sp1(P=0.001)表达及MVD(P=0.001)的状态高度相关。与Sp1表达阴性的患者相比,Sp1表达强阳性的患者高度表达NOSⅢ和MVD。单因素生存分析显示,NOSⅢ、Sp1及MVD高表达提示患者预后较差。多因素Cox比例风险模型显示,NOSⅢ、Sp1高表达以及分期较晚是影响患者预后的独立因素。结论:NOSⅢ在胃癌的血管生成及浸润中可能起重要作用。

Objective：Angiogenesis is a critical step in tumor growth and is regulated by multiple molecular pathways. We evaluated the expression of nitric oxide synthase （NOS） Ⅲ and its relationship with the angiegenic 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 HI and Spl ,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 m expression had close correlation with Spl expression （P =0.001 ） and MVD status （P =0. 001 ）. Patients with positive Spl 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 angiegenesis and infiltration of gastric cancer.