转移抑制基因MKK4在大肠癌中的表达与其生物学行为及预后的关系.DOCVIP

临床医学论文-转移抑制基因MKK4在大肠癌中的表达与其生物学行为及预后的关系 ?????????????????? 作者：王菊芳，何常，陈志英，李珀，钟愉 【摘要】? 　　目的： 检测有丝分裂素激活蛋白激酶激酶4（Mitogenactivated protein Kinase Kinase 4，MKK4)在大肠癌中的表达与其生物学行为及预后的关系。方法： 应用免疫组织化学Envision二步法对58例大肠癌和20例大肠黏膜慢性炎症MKK4表达进行检测。结果： 大肠癌组织中MKK4阳性表达率为75.9 %,慢性炎症组织中MKK4阳性表达率为100 %，大肠癌MKK4阳性表达率较慢性炎症组织低，差异有显著性（P0.05）；大肠癌组织中MKK4阳性表达率与患者年龄、性别、肿瘤部位及大小无关（P0.05），与有无淋巴结转移、临床分期、浸润深度及生存期有关（P0.05）。结论: MKK4可能在大肠癌侵袭转移的发展过程中具有重要作用，与患者预后相关。 【关键词】? 基因 肿瘤抑制 癌 大肠 有丝分裂素激活蛋白激酶激酶类 病理学 临床 预后 　　［Abstract］ Objective: To investigate the expression of mitogenactivated protein kinase kinase 4（MKK4）in colorectal carcinoma and its relationship with the biological behavior and prognosis of the tumor. Methods: MKK4 expression in tissue specimens of 58 cases of colorectal carcinoma and 20 cases of chronic inflammatory were detected by using immunohistochemistry (IHC) method, and Envision twostep staining method. Results: Positive rate of MKK4 protein in colorectal carcinoma tissues ( 75.9 %) was lower than that in chronic inflammatory tissues (100 %). The difference was significant (P0.05). MKK4 expressions in carcinoma tissues correlated with lymph node metastasis（P0.05）, Dukes stage（P0.05）, invasive depth (P0.05), and survival time(P0.05), but not with age, gender, location or tumor volume (P0.05). Conclusions： MKK4 may play an important role in the progression , metastasis of human colorectal carcinoma，and closely correlates with patients prognosis. 　　［Key words］ genes, tumor suppressor; carcinoma; intestine, large; mitogenactivated protein kinase kinases; Pathology, clinical; prognosis 　　转移是肿瘤的主要恶性表型，严重影响肿瘤患者治疗的疗效和预后，肿瘤转移抑制基因的发现为肿瘤转移的诊断和干预治疗提供重要线索。转移抑制基因的功能是当前研究的热点,它们之间一个共同的主题是参与细胞信号转导通路[1]。肿瘤转移抑制基因MKK4/MAP2K4/JNKK1/SEK1(Mitogenactivated protein Kinase Kinase 4/ cJun NH2terminal Kinaseactivating? Kinase1/Stressactivated protein/Erk Kinase 1，MKK4)是应激激活蛋白激酶信号级联反应通路的一员，通过直接激活和（或）磷酸化下游信号，最终调控转录因子的活化，介导机体细胞的生长、分化、存活和凋亡。肿瘤转移抑制基因MKK4不同于肿瘤抑制基因，它抑制转移的发展而不影响原发肿瘤的生长。研究发现原发性肝癌中MKK4 mRNA与MMP9 mRNA的表