Notch1/DLL4信号通路与VEGF在胃癌浸润和转移中的作用及其相关性

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。

The clinical significance and correlation of Notch1/DLL4 pathway and VEGF in invasion and metastasis of gastric carcinoma

Objective： To investigate the expression of Notch1 and its ligand DLL4 in human gastric carcinoma tissues and its correlation with tumor angiogenic metastasis.
Methods：Immunohistochemical SP method was used to detect the expression of Notch1, DLL4 and VEGF in 45 gastric carcinoma tissues and paired adjacent normal gastric mucosa, and the relationship between them and clinico-pathological parameters were analyzed.
Results：The positive expression rate of Notch1, DLL4 and VEGF in gastric carcinoma were higher than that in normal gastric mucosa (P＜0.01). The expression of Notch1 protein in gastric carcinoma was closely related to depth of invasion, lymph node metastasis(P＜0.01) and distant metastasis(P＜0.05). The positive expression rate of DLL4 protein in gastric carcinoma was closely related to depth of invasion(P＜0.01), lymph node metastasis and TNM staging (P＜0.05). The expression of VEGF protein in gastric carcinoma was closely related to depth of invasion(P＜0.01), lymph node metastasis, distant metastasis and TNM staging (P＜0.05).There was a positive correlation between the expressions of Notch1, DLL4 and VEGF(P＜0.05).
Conclusions：The increased expressions of Notch1 and DLL4 in gastric carcinoma is closely related to VEGF and they probably play an important role in tumor angiogenesis, and are involved in invasion and metastasis of gastric carcinoma.