Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
J Surg Oncol. 2012 Mar;105(3):288-92. doi: 10.1002/jso.22097. Epub 2011 Sep 19.
As a well-known pivotal factor of 4E-binding protein 1 (4E-BP1) in controlling cancer proliferation, high expression of its phosphorylated form (p-4E-BP1) has been reported to be associated with poor outcome in various human cancers without pretreated with chemoradiotherapy (CRT). However, no data is available regarding the implication of p-4E-BP1 expression after CRT. Therefore, we conducted this study.
The expression of p-4E-BP1 was semiquantitatively examined with immunohistochemical staining in 60 ypT1T2 esophageal squamous cell carcinoma (SCC) patients and verified by western blot analysis in representative cases. The impact of p-4E-BP1 expression intensity on cancer recurrence and survival was assessed in combination with clinical and pathological descriptors.
The 5-year disease specific survival (DSS) rate of patients with high p-4E-BP1 expression was significantly lower than that of patients with lower p-4E-BP1 expression (5 year DSS: 58% vs. 8.6%, P = 0.00064). Furthermore, in a multivariate analysis by Cox regression model, high p-4E-BP1 expression was confirmed to be an independent prognostic factor (HR: 2.269; unfavorable, P = 0.024) for DSS, while lymph node (HR: 3.016; unfavorable, P = 0.005) was also significant prognostic factor. High p-4E-BP1 expression was specifically associated with locoregional recurrence (LR; P < 0.05). The locoregional control rate reached 97.1% in low p-4E-BP1 tumors.
High p-4E-BP1 expression after CRT is a predictor for LR and worse survival in esophageal SCC patients.
作为调控癌症增殖的关键因子 4E 结合蛋白 1（4E-BP1）的已知靶点，其磷酸化形式（p-4E-BP1）的高表达已被报道与未经放化疗（CRT）预处理的各种人类癌症的不良预后相关。然而，尚无 CRT 后 p-4E-BP1 表达意义的数据。因此，我们开展了此项研究。
采用免疫组化染色法对 60 例 ypT1T2 食管鳞癌（SCC）患者的 p-4E-BP1 表达进行半定量检测，并在代表性病例中采用 Western blot 分析进行验证。结合临床和病理特征评估 p-4E-BP1 表达强度对癌症复发和生存的影响。
高 p-4E-BP1 表达患者的 5 年疾病特异性生存率（DSS）显著低于低 p-4E-BP1 表达患者（5 年 DSS：58%比 8.6%，P=0.00064）。此外，通过 Cox 回归模型的多变量分析，高 p-4E-BP1 表达被确认为 DSS 的独立预后因素（HR：2.269；不利，P=0.024），而淋巴结（HR：3.016；不利，P=0.005）也是显著的预后因素。高 p-4E-BP1 表达与局部区域复发（LR；P<0.05）相关。低 p-4E-BP1 肿瘤的局部区域控制率达到 97.1%。
CRT 后高 p-4E-BP1 表达是食管 SCC 患者 LR 和生存不良的预测因素。
