Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas
Elevated levels of p-Mnk1, p-eIF4E and p-p70S6K proteins are associated with tumor recurrence and poor prognosis in astrocytomas
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DOI：
10.1007/s11060-016-2327-2
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发表时间：
2017-02-01
影响因子：
3.9
通讯作者：
Fan, Songqing
中科院分区：
文献类型：
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作者：
Fan, Weibing;Wang, Weiyuan;Fan, Songqing
恶性星形细胞瘤能够侵犯正常大脑的邻近和远处区域。信号通路改变在星形细胞瘤的发生发展中起重要作用。MNK直接或间接通过PI3K/mTOR/S6K途径对真核细胞翻译起始因子4E(EIF4E)进行去调控，在促进细胞增殖、恶性转化和转移中起重要作用。我们检测并分析了103例星形细胞瘤和54例非肿瘤脑组织中p-Mnk1、p-eIF4E和p-p70S6K蛋白的表达与临床病理特征的关系。结果表明，星形细胞瘤中p-Mnk1和p-eIF4E蛋白过表达的阳性百分率显著高于非肿瘤脑组织(P<；0.05)。P-Mnk1和p-eIF4E升高及三种蛋白共表达与肿瘤复发相关(分别为P=0.003，P=0.006，P=0.007)。P-eIF4E过表达与肿瘤大小显著相关(P=0.019)。P-eIF4E的过度表达和三种蛋白的共同表达与星形细胞瘤的WHO分级有关(P=0.001，P=0.044)。Spearman等级相关分析进一步表明，p-Mnk1和p-eIF4E在星形细胞瘤中的表达呈显著正相关(r=0.294，P=0.003)。此外，p-eIF4E的过度表达以及p-Mnk1、p-eIF4E和p-p70S6K蛋白的共同表达与星形细胞瘤的总生存率呈负相关。多因素COX回归分析进一步证实，p-eIF4E的高表达、三种蛋白的共同表达与星形细胞瘤的预后不良有关，与年龄和WHO分级无关。综上所述，p-eIF4E的过度表达以及p-Mnk1、p-eIF4E和p-p70S6K蛋白的共同表达可作为星形细胞瘤患者预后不良的新的独立生物标志物。
Malignant astrocytomas are able to invade neighboring and distant areas of the normal brain. Signaling pathway alterations play important role in the development of astrocytomas. Deregulation of eukaryotic translation initiation factor 4E (eIF4E) by MAP kinase-interacting kinases (Mnk) on Ser-209 directly or PI3K/mTOR/S6K pathway indirectly has a critical effect on promoting cellular proliferation, malignant transformation and metastasis. We examined and analyzed the correlation between expression of p-Mnk1, p-eIF4E and p-p70S6K proteins and clinicopathological features in 103 astrocytomas and 54 non-tumorous brain tissues. The results indicated that positive percentage of overexpression of p-Mnk1 and p-eIF4E proteins in astrocytomas were significantly higher than that of in the non-tumorous brain tissues (P < 0.05). Elevated p-Mnk1 and p-eIF4E and co-overexpressed three proteins were associated with tumor recurrence (P = 0.003, P = 0.006, P = 0.007, respectively). Overexpressed p-eIF4E significantly correlated with the tumor size (P = 0.019). In addition, overexpression of p-eIF4E and three proteins common expression were related to the WHO grade of astrocytomas (P = 0.001, P = 0.044 respectively). Spearman's rank correlation test further showed that the expression of p-Mnk1 was strongly positive correlated with the expression of p-eIF4E in astrocytomas (r = 0.294, P = 0.003). Besides, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins were inversely correlated with overall survival rates of astrocytomas. Multivariate Cox regression analysis further identified that the elevated p-eIF4E expression, three proteins common expression were correlated with unfavorable prognosis of astrocytomas regardless of ages and WHO grades. Taken together, overexpression of p-eIF4E and co-expression of p-Mnk1, p-eIF4E and p-p70S6K proteins could be used as novel independent poor prognostic biomarkers for patients with astrocytomas.