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A Case-Matched Gender Comparison Transcriptomic Screen Identifies eIF4E and eIF5 as Potential Prognostic Markers in
Matthew P Humphries1, Sreekumar Sundara Rajan1, Alastair Droop1,2
1Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, United Kingdom.
Summary
Male breast cancer (MBC) shows distinct gene expression patterns. Upregulated eIF4E and eIF5 are linked to poorer survival, suggesting translational initiation pathway inhibition as a potential therapy for MBC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Male breast cancer (MBC) is rare but increasingly diagnosed.
- Current treatments for MBC are based on female breast cancer studies, assuming similar biology.
- There is a need to understand gender-specific aspects of breast cancer biology and treatment.
Purpose of the Study:
- To investigate gender-specific gene expression patterns in male breast cancer.
- To identify potential biomarkers for prognosis and therapeutic targets in MBC.
- To evaluate the role of translational initiation factors in MBC.
Main Methods:
- Transcriptomic analysis of male and female breast cancer.
- Immunohistochemical assessment of biomarkers in 697 MBC samples (training and validation sets).
- Quantification of biomarker expression in pre- and posttreatment samples from an MBC patient receiving everolimus and a PI3K/mTOR inhibitor.
Main Results:
- Identified gender-specific gene expression patterns in breast cancer.
- Found eIF4E and eIF5 transcripts upregulated in MBC, negatively correlating with overall survival.
- Demonstrated a marked reduction in eIF4E and eIF5 expression post-treatment with everolimus and PI3K/mTOR inhibitor, correlating with extended survival.
Conclusions:
- Translational initiation pathway inhibition may be clinically useful for MBC patients with high eIF4E and eIF5 expression.
- eIF4E and eIF5 are potential biomarkers for therapeutic intervention in MBC.
- Further independent validation is necessary to confirm these findings for clinical application.
