Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma.
Phosphorylated Mnk1 and eIF4E are associated with lymph node metastasis and poor prognosis of nasopharyngeal carcinoma.
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磷酸化 Mnk1 和 eIF4E 与鼻咽癌淋巴结转移和不良预后相关
DOI：
10.1371/journal.pone.0089220
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Fan S
中科院分区：
文献类型：
--
作者：
Zheng J;Li J;Xu L;Xie G;Wen Q;Luo J;Li D;Huang D;Fan S
鼻咽癌是一种在世界大部分地区罕见，但在东南亚特别是中国南部地区常见的头颈部恶性肿瘤。真核细胞翻译起始因子4E(EIF4E)被丝氨酸蛋白-209(Ser-209)上的丝氨酸蛋白激酶相互作用蛋白(MNK)磷酸化，促进细胞增殖、存活、恶性转化和转移。然而，p-eIF4E和p-Mnk1蛋白表达的改变是否与鼻咽癌的临床病理和预后有关，尚未见报道。本研究应用免疫组织化学方法检测鼻咽癌组织和非癌鼻咽上皮组织中p-eIF4E和p-Mnk1蛋白的表达，探讨p-eIF4E和p-Mnk1蛋白表达与鼻咽癌临床病理特征的关系。结果表明，p-Mnk1和p-eIF4E蛋白在鼻咽癌组织中的阳性表达率(83.5%和75.4%)显著高于非癌鼻咽上皮(40.0%和32.9%)。P-eIF4E和p-Mnk1在有颈淋巴结转移的鼻咽癌组织中的阳性表达明显高于无颈淋巴结转移的鼻咽癌组织。此外，p-eIF4E在转移性鼻咽癌中的表达比匹配的原发鼻咽癌更明显。P-eIF4E和p-Mnk1的表达增加与总生存期呈显著负相关。Spearman等级相关检验进一步显示p-Mnk1和p-eIF4E在鼻咽癌中的表达呈显著正相关。多因素分析显示，p-Mnk1和p-eIF4E的表达与鼻咽癌的淋巴结转移、临床分期、放化疗组合、组织学类型、年龄和性别无关，是独立的预后因素。综上所述，p-Mnk1和p-eIF4E的高表达可能是预测鼻咽癌预后不良的新的有价值的生物标志物，并为制定有效的治疗策略提供治疗靶点。
Nasopharyngeal carcinoma (NPC) is a head and neck malignant tumor rare throughout most of the world but common in Southeast Asia, especially in Southern China. The phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 promotes cellular proliferation, survival, malignant transformation and metastasis. However, whether the alterations of the expression of p-eIF4E and p-Mnk1 protein are associated with clinicopathologic/prognostic implication for NPC has not been reported. The purposes of the present study are to examine the expression of p-eIF4E and p-Mnk1 protein in NPC and non-cancerous nasopharyngeal epithelial tissues by immunohistochemistry and evaluate the association between the expression of p-eIF4E and p-Mnk1 protein and clinicopathological characteristics of NPC. The results showed that the positive percentage of p-Mnk1 and p-eIF4E proteins expression in NPC (83.5% and 75.4%, respectively) was significantly higher than that in non-cancerous nasopharyngeal epithelium (40.0% and 32.9%, respectively). The positive expression of p-eIF4E and p-Mnk1 in the NPC with cervical lymph node metastasis was significantly higher than those without lymph node metastasis. Additionally, p-eIF4E expression was more pronouncedly increased in metastatic NPC than the matched primary NPC. Increase of p-eIF4E and p-Mnk1 expression was significantly correlated inversely with overall survival. Spearman’s rank correlation test further showed that expression of p-Mnk1 was strongly positive correlated with expression of p-eIF4E in NPC. The expression of p-Mnk1 and p-eIF4E in NPC was proved to be the independent prognostic factors regardless of lymph node metastasis, clinical stages and combination of radiotherapy and chemotherapy, histological type, age and gender by multivariate analysis. Taken together, high expression of p-Mnk1 and p-eIF4E might be novel valuable biomarkers to predict poor prognosis of NPC and therapeutic targets for developing the valid treatment strategies.
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DOI：
10.1002/hed.20833
发表时间：
2008-07
影响因子：
2.9
作者：
Chou, Josephine;Lin, Yu-Ching;Kim, Jae;You, Liang;Xu, Zhidong;He, Biao;Jablons, David M.
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1005320107
发表时间：
2010-08-10
影响因子：
11.1
作者：
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Sonenberg, Nahum
影响因子：
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Lee, C. -C.;Chu, S. -T.;Chen, L. -F.
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