Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis
Loss of RUNX3 expression significantly affects the clinical outcome of gastric cancer patients and its restoration causes drastic suppression of tumor growth and metastasis
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DOI：
10.1158/0008-5472.can-04-3741
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发表时间：
2005-06-01
期刊：
影响因子：
11.2
通讯作者：
Xie, KP
中科院分区：
文献类型：
--
作者：
Wei, DY;Gong, WD;Xie, KP
确定精确的预后标志物和有效的治疗靶点是胃癌治疗的关键。在本研究中，我们确定了胃癌细胞和胃癌标本中RUNX3的表达水平及其变化对癌症生物学和临床结果的影响。与正常胃粘膜相比，86例胃肿瘤中RUNX3蛋白表达缺失或显着降低（P < 0.0001），这与较差的生存时间显着相关（P = 0.0005）。在 Cox 比例风险模型中，RUNX3 表达独立预测更好的生存率 (P = 0.036)。此外，各种人胃癌细胞系也表现出RUNX3表达的丧失或急剧下降。强制恢复 RUNX3 表达会导致细胞周期蛋白 D1 下调，但导致 p27、caspase 3、7 和 8 表达上调、细胞周期停滞和体外细胞凋亡，并在动物模型中显着减弱肿瘤生长并消除转移。因此，我们提供了临床和机制证据，表明RUNX3是胃癌的独立预后因素和潜在的治疗靶点。
Identification of precise prognostic marker and effective therapeutic target is pivotal in the treatment of gastric cancer. In the present study, we determined the level of RUNX3 expression in gastric cancer cells and gastric cancer specimens and the impact of its alteration on cancer biology and clinical outcome. There was a loss or substantial decrease of RUNX3 protein expression in 86 cases of gastric tumors as compared with that in normal gastric mucosa (P < 0.0001), which was significantly associated with inferior survival duration (P = 0.0005). In a Cox proportional hazards model, RUNX3 expression independently predicted better survival (P = 0.036). Moreover, various human gastric cancer cell lines also exhibited loss or drastic decrease of RUNX3 expression. Enforced restoration of RUNX3 expression led to down-regulation of cyclin D1 but to up-regulation of p27, caspase 3, 7, and 8 expression, cell cycle arrest, and apoptosis in vitro, and dramatic attenuation of tumor growth and abrogation of metastasis in animal models. Therefore, we offered both clinical and mechanistic evidence that RUNX3 was an independent prognostic factor and a potential therapeutic target for gastric cancer.