title: 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: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  High p-4E-BP1 expression after CRT is a predictor for LR and worse survival in esophageal SCC patients.
authors.affiliation: Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yin-Kai
authors.initials: YK
authors.lastname: Chao
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chuang
authors.forename: Chi-Ju
authors.initials: CJ
authors.lastname: Yeh
authors.forename: Yu-Sun
authors.initials: YS
authors.lastname: Chang
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Wu
authors.forename: Shao-Yun
authors.initials: SY
authors.lastname: Kuo
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D018797:Cell Cycle Proteins; D059248:Chemoradiotherapy; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D012189:Retrospective Studies
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins