EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma.
EIF4EBP1 overexpression is associated with poor survival and disease progression in patients with hepatocellular carcinoma.
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EIF4EBP1 过度表达与肝细胞癌患者的生存率低和疾病进展相关。
DOI：
10.1371/journal.pone.0117493
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Wang HY
中科院分区：
文献类型：
--
作者：
Cha YL;Li PD;Yuan LJ;Zhang MY;Zhang YJ;Rao HL;Zhang HZ;Zheng XF;Wang HY
EIF 4 EBP 1在mTOR信号通路中起重要作用。研究表明，EIF 4 EBP 1在癌症发生中起着关键作用。然而，EIF 4 EBP 1在肝细胞癌（HCC）中的临床意义和生物学作用尚未阐明。因此，我们的目的是探讨EIF 4 EBP 1在肝癌中的临床意义。共纳入128例HCC患者。分别采用qRT-PCR、Western blot和免疫组化法检测HCC组织中EIF 4 EBP 1的表达。分析EIF 4 EBP 1表达与胃癌临床特征及生存期的关系。60%（24/40）新鲜肝癌组织中EIF 4 EBP 1 mRNA的表达水平显著高于癌旁正常肝组织（P = 0.044）。免疫组化结果显示，EIF 4 EBP 1蛋白在88例（53%，47/88）石蜡包埋的HCC组织中表达显著高于相应的NCL组织（P < 0.001）。HCC组织中EIF 4 EBP 1蛋白表达与血清AFP显著相关（P = 0.003），与病理分级（P = 0.085）、肿瘤数目（P = 0.084）、癌栓（P = 0.084）和包膜（P = 0.073）轻微相关。EIF 4 EBP 1蛋白高表达患者的5年总生存率（40.3% vs 73.6%）和5年无病生存率（33.0% vs 49.0%）明显低于低表达患者。此外，考克斯回归分析显示，EIF 4 EBP 1蛋白是HCC患者总生存期（HR，2.285; 95% CI，1.154-4.527; P = 0.018）和无病生存期（HR，1.901; 95% CI，1.067-3.386; P = 0.029）的独立预后因素。本研究首次证实EIF 4 EBP 1 mRNA和蛋白在HCC组织中表达显著上调，且EIF 4 EBP 1蛋白的过表达与HCC患者的预后不良和疾病进展密切相关，为HCC患者的预后评估提供了新的指标和治疗靶点。
EIF4EBP1 acts as a crucial effector in mTOR signaling pathway. Studies have suggested that EIF4EBP1 plays a critical role in carcinogenesis. However, the clinical significance and biological role of EIF4EBP1 in hepatocellular carcinoma (HCC) have not been elucidated. Therefore, we aimed to investigate the clinical significance of EIF4EBP1 in HCC. Total 128 cases of HCCs were included in this study. EIF4EBP1 expression in HCC tissues was detected by qRT-PCR, Western blot and immunohistochemistry, respectively. Then the relationships between EIF4EBP1 expression and clinical features as well as survival were analyzed. The expression level of EIF4EBP1 mRNA is significantly higher in 60% (24/40) of fresh HCC tissues than that in the matched adjacent nontumor liver (NCL) tissues (P = 0.044). Similarly, EIF4EBP1 protein is notably upregulated in 8 HCC tissues (randomly selected from the 40 HCCs) measured by Western blot and is significantly increased in another 88 paraffin-embedded HCCs (53%, 47/88) by immunohistochemistry compared with the matched NCLs (P < 0.001). EIF4EBP1 protein expression in HCC tissues is significantly correlated with serum AFP (P = 0.003) and marginally significantly associated with pathological grade (P = 0.085), tumor number (P = 0.084), tumor embolus (P = 0.084) and capsulation (P = 0.073). Patients with higher EIF4EBP1 protein expression have a much worse 5-year overall survival (40.3% vs 73.6%) and 5-year disease-free survival (33.0% vs 49.0%) than those with low expression. Furthermore, Cox regression analysis shows that EIF4EBP1 protein is an independent prognostic factor for overall survival (HR, 2.285; 95% CI, 1.154–4.527; P = 0.018) and disease-free survival (HR, 1.901; 95% CI, 1.067–3.386; P = 0.029) in HCC patients. Our results demonstrate for the first time that EIF4EBP1 mRNA and protein are markedly up-regulated in HCC tissues, and the protein overexpression is significantly associated with poor survival and progression, which provide a potential new prognostic marker and therapeutic target for HCC patients.
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影响因子：
6.2
作者：
Castellvi, Josep;Garcia, Angel;Ramon y Cajal, Santiago
通讯作者：
Ramon y Cajal, Santiago
DOI：
10.1073/pnas.0914856107
发表时间：
2010-02-09
影响因子：
11.1
作者：
Aoyagi, Mariko;Gaspar, Miguel;Shenk, Thomas E.
通讯作者：
Shenk, Thomas E.
影响因子：
11.5
作者：
Rojo, Federico;Najera, Laura;Ramon y Cajal, Santiago
通讯作者：
Ramon y Cajal, Santiago
DOI：
10.4161/cc.25099
发表时间：
2013-07-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Wang C;Cigliano A;Delogu S;Armbruster J;Dombrowski F;Evert M;Chen X;Calvisi DF
通讯作者：
Calvisi DF
影响因子：
4.8
作者：
Scheper, GC;Mulder, J;vanWijk, R
通讯作者：
vanWijk, R