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目的探讨Notch1和其配体DLL4蛋白在胃癌组织中的表达及其与肿瘤血管转移之间的关系。方法采用免疫组织化学SP法检测45例胃癌及25例癌旁正常组织中Notch1,DLL4,VEGF的表达情况,并分析它们与各临床病理参数的关系。结果Notch1,DLL4,VEGF蛋白在胃癌中表达的阳性率均明显高于正常胃黏膜组织,差异均有统计学意义(P<0.01)。Notch1蛋白在胃癌中表达与肿瘤浸润深度、淋巴结转移(P<0.01)及远处转移(P<0.05)有关;DLL4蛋白在胃癌中表达与肿瘤浸润深度(P<0.01),淋巴结转移及临床分期(P<0.05)有关;VEGF蛋白在胃癌中表达与浸润深度(P<0.01)、淋巴结转移、远处转移及TNM分期(P<0.05)有关,上述各因素分组间差异有统计学意义。Notch1,DLL4,VEGF蛋白的表达三者两两间均呈正相关关系(rs=0.355,rs=0.367,rs=0.334;均P<0.05)。结论Notch1/DLL4受体通路在胃癌组织中的表达上调与血管内皮生长因子有关,它们可能共同调控肿瘤新生血管形成,参与胃癌的侵袭和转移。
Objective To investigate the expression of Notch1 and its ligand DLL4 in gastric carcinoma and its relationship with tumor vessel metastasis. Methods The expressions of Notch1, DLL4 and VEGF in 45 cases of gastric cancer and 25 cases of adjacent normal tissues were detected by immunohistochemical SP method and their relationship with clinicopathological parameters were analyzed. Results The positive rates of Notch1, DLL4 and VEGF in gastric cancer were significantly higher than those in normal gastric mucosa (P <0.01). The expression of Notch1 protein in gastric carcinoma was correlated with the depth of invasion, lymph node metastasis (P <0.01) and distant metastasis (P <0.05). The expression of DLL4 protein in gastric carcinoma was significantly correlated with the depth of tumor invasion (P <0.01), lymph node metastasis and clinical stage (P <0.05). The expression of VEGF in gastric cancer was related to the depth of invasion (P <0.01), lymph node metastasis, distant metastasis and TNM stage (P <0.05). There was significant difference among the above groups. The expressions of Notch1, DLL4 and VEGF were positively correlated with each other (rs = 0.355, rs = 0.367, rs = 0.334; all P <0.05). Conclusions The upregulation of Notch1 / DLL4 receptor pathway in gastric cancer is associated with vascular endothelial growth factor. They may regulate tumor angiogenesis and participate in the invasion and metastasis of gastric cancer.