Lee Hyoun Wook, Park Moon-Il, Kim Mee-Seon, Kim Seok-Hyun, Roh Mee Sook, Kim Kyungeun, Jung Sang Bong, Lee Eun Hee
Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
Pathol Res Pract. 2015 Apr;211(4):298-302. doi: 10.1016/j.prp.2014.12.015. Epub 2015 Jan 21.
Multiple intracellular transforming signals regulate eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP1). The signals result in hierarchical phosphorylation of 4E-BP1, resulting in release of eIF4E, relieving translational repression and enhancing oncogenic protein synthesis. This study assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in gastric cancer and its correlation with clinicopathological parameters and patient survival. Tissue microarray blocks were generated from 179 gastric carcinomas and immunohistochemically stained for p-4E-BP1. The expression of p-4E-BP1 was higher in tumors that were intestinal-type (P=0.028); had a diameter smaller than 5cm (P=0.001); were lower pathological T stage (P<0.001), N stage (P=0.004), or TNM stage (P<0.001); did not have distant metastasis (P=0.027). High p-4E-BP1 expression significantly correlated with prolonged overall survival (P=0.046) and disease-free survival (P=0.035), but was not an independent prognostic factor in multivariate analysis. Our results indicate that p-4E-BP1 is more highly expressed in early gastric cancers than in advanced ones, and has limited potential as an independent prognostic biomarker in patients with gastric cancer. Larger well-controlled studies with molecular validation are warranted to elucidate more exact prognostic significance and working mechanism of p-4E-BP1 in gastric cancer.
多种细胞内转化信号调节真核生物翻译起始因子4E（eIF4E）结合蛋白（4E-BP1）。这些信号导致4E-BP1的分级磷酸化，从而使eIF4E释放，解除翻译抑制并增强致癌蛋白的合成。本研究评估了磷酸化4E-BP1（p-4E-BP1）在胃癌中的表达及其与临床病理参数和患者生存的相关性。从179例胃癌中制作组织微阵列块，并对p-4E-BP1进行免疫组织化学染色。p-4E-BP1在肠型肿瘤中表达较高（P=0.028）；直径小于5cm（P=0.001）；病理T分期较低（P<0.001）、N分期（P=0.004）或TNM分期（P<0.001）；无远处转移（P=0.027）。高p-4E-BP1表达与总生存期延长（P=0.046）和无病生存期延长（P=0.035）显著相关，但在多变量分析中不是独立的预后因素。我们的结果表明，p-4E-BP1在早期胃癌中的表达高于晚期胃癌，并且作为胃癌患者独立预后生物标志物的潜力有限。有必要进行更大规模的、经过良好对照且有分子验证的研究，以阐明p-4E-BP1在胃癌中更确切的预后意义和作用机制。
