Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer. Academic Article uri icon

Overview

abstract

  • PURPOSE: The eukaryotic translation initiation factor complex 4E (eIF4E) is downstream in the mammalian target of rapamycin (mTOR) pathway. This study explored expression of eIF4E and its relationship with the PTEN/AKT and RAS/MEK/ERK pathways in non-small cell lung carcinoma (NSCLC). EXPERIMENTAL DESIGN: The status of phosphorylated eIF4E (p-eIF4E), phosphorylated AKT (p-AKT), PTEN, phosphorylated tuberin (p-TSC2), phosphorylated mTOR (p-mTOR), phosphorylated S6 (p-S6), and phosphorylated Erk1/2 (p-Erk1/2) was studied using immunohistochemical analysis applied to a tissue microarray containing 300 NSCLCs. Staining results for each antibody were compared with clinical and pathologic features, and the relationship between staining results was explored. RESULTS: Overexpression of p-eIF4E, p-AKT, p-TSC2, p-mTOR, p-S6, and p-Erk1/2 in NSCLC was found in 39.9%, 78.8%, 5.1%, 46.7%, 27.1%, and 16.6% of tumors, respectively. The phenotype of p-eIF4E correlated positively with that of p-AKT, p-TSC2, and p-S6 (P < 0.001). Overall survival in NSCLC patients was significantly shorter in cases with overexpression of p-eIF4E and p-AKT alone and in combination (log-rank P < 0.001, each). Cases with underexpression of PTEN were limited (6.4%), and this phenotype did not correlate with any clinical variable. In cluster analysis, the p-AKT/p-mTOR/p-eIF4E/p-S6-positive group had significantly shorter survival compared with the survival of all cases (P < 0.001). Multivariate analysis showed that p-eIF4E overexpression is an independent prognostic factor for NSCLC (P = 0.004). CONCLUSIONS: This study shows that p-eIF4E expression in addition to p-AKT predicts poor prognosis in NSCLC. Moreover, the correlation between expression of p-eIF4E with p-AKT, as well as p-TSC2 and p-S6, indicates that eIF4E activation through the AKT pathway plays an important role in the progression of NSCLC.

publication date

  • December 15, 2009

Research

keywords

  • Carcinoma, Non-Small-Cell Lung
  • Eukaryotic Initiation Factor-4E
  • Lung Neoplasms
  • Proto-Oncogene Proteins c-akt

Identity

PubMed Central ID

  • PMC7581274

Scopus Document Identifier

  • 74949114784

Digital Object Identifier (DOI)

  • 10.1158/1078-0432.CCR-09-0986

PubMed ID

  • 20008839

Additional Document Info

volume

  • 16

issue

  • 1