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首页> 外文期刊>Oncology reports >Clinicopathological significance of N-cadherin and VEGF in advanced gastric cancer brain metastasis and the effects of metformin in preclinical models
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Clinicopathological significance of N-cadherin and VEGF in advanced gastric cancer brain metastasis and the effects of metformin in preclinical models

机译：N-钙粘着蛋白和VEGF在晚期胃癌脑转移中的临床病理意义以及二甲双胍在临床前模型中的作用

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Gastric cancer is the second most common cause of cancer-related death worldwide. Although brain metastasis is a rare complication of gastric cancer, no standard therapy for gastric cancer brain metastasis has been established. We attempted to identify biological markers that predict brain metastasis, and investigated how to modulate such markers. A case-control study of patients newly diagnosed with gastric cancer who had developed brain metastasis during follow-up, was conducted. These patients were compared with patients who had advanced gastric cancer but no evidence of brain metastasis. Immunohistochemistry was used to analyze the expression of E-cadherin, N-cadherin, MSS1, claudin-3, claudin-4, Glut1, clusterin, ITGB4, vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR) and p53. The expression of VEGF tended to be higher in the case group (33.3 vs. 0%, p=0.055). Median survival was significantly correlated with vascular invasion (12 vs. 33 months, p=0.008) and N-cadherin expression (36 vs. 12 months, p=0.027). We also investigated the effects of metformin in tumor-bearing mouse models. VEGF expression was decreased and E-cadherin increased in the metformin-treated group when compared with the control group. The expression of the mesenchymal marker MMP9 was decreased in the metformin-treated group. Brain metastasis of advanced gastric cancer was associated with the expression of VEGF. Metformin treatment may be useful for modulating the metastatic capacity by reducing VEGF expression and blocking epithelial-to-mesenchymal transition.
机译：胃癌是全世界与癌症相关的死亡的第二大最常见原因。尽管脑转移是胃癌的罕见并发症，但尚未建立胃癌脑转移的标准疗法。我们试图鉴定可预测脑转移的生物学标志物，并研究如何调节这些标志物。进行了一项病例对照研究，对在随访期间发生脑转移的新诊断为胃癌的患者进行研究。将这些患者与患有晚期胃癌但无脑转移证据的患者进行比较。免疫组化分析E-钙粘蛋白，N-钙粘蛋白，MSS1，claudin-3，claudin-4，Glut1，Clusterin，ITGB4，血管内皮生长因子（VEGF），表皮生长因子受体（EGFR）和p53的表达。病例组中VEGF的表达倾向于较高（33.3 vs. 0％，p = 0.055）。中位生存期与血管浸润（12个月对33个月，p = 0.008）和N-钙粘蛋白表达（36个月对12个月，p = 0.027）显着相关。我们还研究了二甲双胍在荷瘤小鼠模型中的作用。与对照组相比，二甲双胍治疗组的VEGF表达降低，而E-cadherin增加。在二甲双胍治疗组中，间充质标记物MMP9的表达降低。晚期胃癌的脑转移与VEGF的表达有关。二甲双胍治疗可通过减少VEGF表达并阻断上皮向间充质转化而用于调节转移能力。

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