Overexpression of phosphorylated 4E-binding protein 1 and its clinicopathological significances in gastric cancer

Pathol Res Pract. 2015 Apr;211(4):298-302. doi: 10.1016/j.prp.2014.12.015. Epub 2015 Jan 21.

Abstract

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.

Keywords: Gastric cancer; Immunohistochemistry; Prognosis; p-4E-BP1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cell Cycle Proteins
  • Disease-Free Survival
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Prognosis
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tissue Array Analysis

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers, Tumor
  • Cell Cycle Proteins
  • EIF4EBP1 protein, human
  • Phosphoproteins