High expression of phosphorylated 4E-binding protein 1 is an adverse prognostic factor in esophageal squamous cell carcinoma.
Cell signaling pathways play important roles in oncogenesis. Among a large number of signaling regulators in different pathways, 4E-binding protein 1 (4E-BP1) was found to be a key factor, which converges several oncogenic signals, phosphorylates the molecules, and drives the downstream proliferative signals. Recent studies showed that high expression of phosphorylated 4E-BP-1 (p-4E-BP1) is associated with poor prognosis, tumor progression, or nodal metastasis in different human cancers, but its prognostic significance in esophageal cancer remains undefined. In this study, we investigated the expression levels of p-4E-BP1 with two different phosphorylation sites Thr(37/46) and Thr(70) by immunohistochemistry and their prognostic significance in 78 cases of surgically resected esophageal squamous cell carcinoma (SCC) for the first time. We found no correlation of p-4E-BP1 expression with age, gender, preoperative concurrent chemoradiotherapy, tumor grade, pT classification, pN, pM, or pStage. Multivariate Cox regression analysis showed that high expression of p-4E-BP-1 Thr(37/46) was an independent adverse prognostic factor, with a hazard ratio of 1.73 (95% confidence interval = 1.03-2.90) and a p value of 0.038. Stratifying the patients with other prognostic factors, we found that the effect of p-4E-BP1 Thr(37/46) on survival was significant only in patients with relatively early stage disease (pT1/pT2, pN0, or pStage I/II; p = 0.0047, 0.012, and 0.011, respectively). Our data suggest that assessment of p-4E-BP1 expression could identify a subpopulation of earlier stage esophageal SCC patients with poor prognosis. These patients could be possible candidates for future studies on more aggressive treatment or target therapy.
Department of Pathology, Chang Gung Memorial Hospital, Linko, Chang Gung University College of Medicine, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, 333, Taiwan.
Chi-Ju
CJ
Yeh
Wen-Yu
WY
Chuang
Yin-Kai
YK
Chao
Yun-Hen
YH
Liu
Yu-Sun
YS
Chang
Shao-Yun
SY
Kuo
Chen-Kan
CK
Tseng
Hsien-Kun
HK
Chang
Chuen
C
Hsueh
D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D018797:Cell Cycle Proteins; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010750:Phosphoproteins / Q000096:biosynthesis*; D010766:Phosphorylation; D011379:Prognosis; D016016:Proportional Hazards Models
D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins