Prognostic significance of eukaryotic initiation factor 4E in hepatocellular carcinoma

J Cancer Res Clin Oncol. 2016 Nov;142(11):2309-17. doi: 10.1007/s00432-016-2232-2. Epub 2016 Sep 6.

Abstract

Purpose: Aberrant expression of eukaryotic initiation factor 4E (eIF4E) has been observed in human malignancies. However, its role in hepatocellular carcinoma (HCC) remains to be established. The purpose of this study was to detect eIF4E expression and to evaluate its clinical relevance.

Methods: The eIF4E expression was studied in ninety HCC and randomly selected thirty-one non-tumor tissues from the same patient cohort, as well as in normal hepatic and HCC cell lines. The relation between its expression and clinicopathological parameters was also analyzed.

Results: eIF4E expression was higher in HCC samples and cell lines compared with that in non-tumor tissues (P < 0.001) and hepatocyte LO2, respectively. eIF4E overexpression was significantly associated with tumor number (P = 0.005) and incomplete encapsulation (P = 0.001). The 5-year overall survival rate and disease-free survival rate for patients with high eIF4E expression were 32.5 and 31.2 %, respectively; and for low eIF4E expression, it was 67.9 and 64.4 %, respectively (P < 0.001). Furthermore, subgroup analysis showed that high eIF4E level predicted poorer overall survival only for incomplete encapsulation (P = 0.001) and cirrhosis (P < 0.001), but not for complete encapsulation (P = 0.804) and non-cirrhosis (P = 0.359). Multivariate analysis revealed that eIF4E overexpression was an independent indicator for both overall survival (hazard ratio, 2.015; P = 0.043) and disease-free survival (hazard ratio, 2.666; P = 0.006).

Conclusions: eIF4E protein might result in the malignant progression of HCC, and its overexpression may be a powerful prognostic biomarker and therapeutic target for HCC patients.

Keywords: Clinicopathological feature; Eukaryotic initiation factor 4E; Hepatocellular carcinoma; Prognostic biomarker; Tissue microarray.

MeSH terms

  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Disease Progression
  • Female
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Nucleocytoplasmic Transport Proteins / biosynthesis
  • Nucleocytoplasmic Transport Proteins / metabolism*
  • Prognosis
  • Survival Rate
  • Tissue Array Analysis
  • Up-Regulation

Substances

  • EIF4ENIF1 protein, human
  • Nucleocytoplasmic Transport Proteins