The prognostic value of altered eIF3a and its association with p27 in non-small cell lung cancers

PLoS One. 2014 Apr 30;9(4):e96008. doi: 10.1371/journal.pone.0096008. eCollection 2014.

Abstract

Background: Over-expressed eukaryotic initiation factor 3a (eIF3a) in non-small cell lung cancer (NSCLC) contributed to cisplatin sensitivity. However, the role of eIF3a in oncogenesis was still controversial. This study was designed to investigate the prognostic impact of eIF3a and p27 in radically resected NSCLC patients.

Methods: The expression levels of subcellular eIF3a and p27 were evaluated immunohistochemically in 537 radically resected NSCLC samples, and another cohort of 210 stage II NSCLC patients. Disease specific survival (DSS) and disease free survival (DFS) were analyzed by Kaplan-Meier method and Cox regression model.

Results: The subcellular expression of eIF3a was strongly correlated with status of p27 (Spearman rank coefficient correlation for cytoplasmic eIF3a and p27=0.653, for nuclear staining=0.716). Moreover, survival analysis revealed favorable prognostic impact of nuclear eIF3a, p27, and the combination high nuclear staining on NSCLC (Hazards Ratio=0.360, 95%CI=0.109-0.782, P=0.028). In addition, interaction research between biomarkers and chemotherapy status disclosed cisplatin-based regimen trend to prolong DSS of stage II NSCLC patients with high eIF3a-C (P=0.036)and low p27-N (P=0.031).

Conclusions: Our findings suggested altered eIF3a expression closely correlated with p27 status, and the association was of prognostic value for resected NSCLC. Altered expression of eIF3a and p27 predicted prognosis of NSCLC independently.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Eukaryotic Initiation Factor-3 / metabolism*
  • Female
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Prognosis

Substances

  • EIF3A protein, human
  • Eukaryotic Initiation Factor-3
  • Cyclin-Dependent Kinase Inhibitor p27

Grants and funding

This work was supported by National High-tech R&D Program of China 863 Program Grant 2012AA02A517 (Z. Liu), Program for the Special Scientific Research Foundation of Doctor Disciplines in University of Ministry of Education of China Grant 20110162110034 (Z. Liu), National Natural Science Foundation of China Grants 30873089, 81173129 (Z. Liu), 81202595 (J. Yin), Hunan Provincial Natural Science Foundation 12JJ7006 (Z. Liu), Anhui Provincial Natural Science Foundation 1408085MH163 (J. Shen). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.