MNK2作为非小细胞肺癌的预后因子及其分子基础

项目名称： MNK2作为非小细胞肺癌的预后因子及其分子基础

项目编号： No.81201847

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 肿瘤学2

项目作者： 吴其年

作者单位： 广州医科大学

项目金额： 23万元

中文摘要： MAP kinase-interacting kinase-2 (MNK2) 是MAP激酶蛋白通路的下游激酶，通过磷酸化真核细胞起始因子4E (eIF4E)促进细胞生长。已有研究表明MNK2在乳腺癌及淋巴瘤的发生中有癌基因的功能，是药物治疗的潜在靶点，但MNK2在非小细胞肺癌中是否有癌基因的功能及其与患者预后的关系尚未见报道。我们的前期研究分析了50例首次诊断为非小细胞肺癌并有完整临床病理资料的病例，初步结果表明非小细胞肺癌组织中MNK2的蛋白表达水平可作为独立的不良预后因子。本项目将病例数增加至250-300例，分析MNK2与患者预后及临床病理特征的关系，进一步证实MNK2作为非小细胞肺癌预后因子及其预测效果，而后通过细胞株及裸鼠实验证明MNK2在非小细胞肺癌中有促进细胞生长、抑制细胞凋亡等作用。从细胞、动物及临床三个水平证实MNK2可作为非小细胞肺癌独立预后因子及基因治疗潜在靶点。

中文关键词： 非小细胞肺癌；MNK2；预后；靶基因；

英文摘要： MNK2 (MAP kinase-interacting kinase 2) are protein-serine/threonine kinases that are activated by ERK2 or p38 and phosphorylate eIF4E, which is involved in cap-dependent translation initiation.There are study demonstrate an oncogenic role for Mnk2 in tumor development, and highlight these molecules as potential anticancer drug targets that could be inactivated with minimal side effects.but there are gaps in our knowledge of the relation between MNK2 expression level and patients prognosis and how it regulated and function in non-small-cell lung carcinoma(NSCLC). We had analyzed 50 cases which diognosed NSCLC first with completely follow up, clinicopathological data, it indicate that is associated with poor prognosis of NSCLC and may serve as an independent prognostic marker. We will add the case to 250-300, analyze the relation between MNK2 expression level and clinicopathological characteristics, to verification MNK2 as a prognostic factor and the senstive and specificity. Then to demonstrate the promoting and apoptosis inhibition role of MNK2 in NSCLC by cell lines and nude mice experiments. This study will acknowledge that MNK2 serve as an independent prognostic factor and potential gene therapy target.

英文关键词： non-small cell lung cancer；MNK2；prognosis；target gene；