High phosphorylated 4E‐binding protein 1 expression after chemoradiotherapy is a predictor for locoregional recurrence and worse survival in esophageal squamous cell carcinoma patients

Abstract

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.