Eukaryotic translation initiation factor 4E (eIF4E) expression is associated with breast cancer tumor phenotype and

Tuomas Heikkinen1, Taina Korpela, Rainer Fagerholm

  • 1Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Biomedicum Helsinki, P.O. Box 700, 00029 Helsinki, Finland. tuomas.heikkinen@helsinki.fi

Insights

High expression of eukaryotic initiation factor eIF4E in breast tumors correlates with aggressive traits and poorer survival. This effect is amplified in patients receiving anthracycline chemotherapy, suggesting eIF4E

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Aberrant mRNA translation is a hallmark of carcinogenesis, impacting proteins crucial for tumor development.
  • Eukaryotic initiation factor eIF4E regulates translation of cancer-related transcripts; its altered expression is linked to various cancers and reduced patient survival.

Purpose of the Study:

  • To investigate the association between eIF4E protein levels and breast tumor characteristics.
  • To evaluate the prognostic significance of eIF4E expression on patient survival, considering adjuvant chemotherapy.
  • To explore eIF4E's potential as a predictive marker for anthracycline chemotherapy response.

Main Methods:

  • Immunohistochemistry (IHC) was used to quantify eIF4E protein levels in 1,233 breast tumor samples.
  • Tissue microarrays were utilized for high-throughput analysis.
  • Statistical analyses, including multivariate analysis and subgroup analysis by chemotherapy treatment, were performed.

Main Results:

  • High eIF4E expression was significantly associated with aggressive tumor features: higher grade, receptor negativity (ER, PR), HER2 positivity, elevated p53 and Ki67, and triple-negative subtype.
  • Elevated eIF4E levels predicted worse breast cancer-specific survival (HR=1.99) and were an independent prognostic factor.
  • The survival impact of high eIF4E was most pronounced in patients treated with anthracycline chemotherapy (HR=3.34), with no significant effect in non-anthracycline treated groups.

Conclusions:

  • High eIF4E protein expression is linked to adverse breast cancer characteristics and predicts poor survival.
  • eIF4E expression may serve as a predictive biomarker for anthracycline chemotherapy efficacy.
  • Further research is warranted to explore eIF4E's role as a therapeutic target and predictive factor.

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