SPAG5 as a prognostic biomarker and chemotherapy sensitivity predictor in breast cancer: a retrospective, integrated...

Area of Science:

• Genomics and Molecular Biology
• Oncology
• Biomarker Discovery

Background:

• Proliferation markers are crucial for guiding breast cancer systemic treatments.
• The optimal molecular marker for predicting treatment response remains unidentified.
• This study aimed to identify proliferation drivers and their clinical outcome associations.

Purpose of the Study:

• To identify key genes driving breast cancer proliferation.
• To assess the prognostic and predictive value of SPAG5 in breast cancer.
• To evaluate SPAG5 as a potential biomarker for chemotherapy response.

Main Methods:

• Utilized an artificial neural network-based integrative data mining approach across three patient cohorts.
• Identified Sperm-associated antigen 5 (SPAG5) as a key gene in the proliferation interactome map.
• Investigated SPAG5 gene copy number aberrations, mRNA, and protein expression in multiple breast cancer cohorts.

Main Results:

• SPAG5 gene gain/amplification and high transcript/protein levels correlated with shorter breast cancer-specific survival.
• High SPAG5 expression was independently associated with reduced survival in multivariable analyses.
• High SPAG5 protein expression predicted improved survival with anthracycline chemotherapy in ER-negative breast cancer.
• High SPAG5 transcript levels predicted longer relapse-free survival with taxane/anthracycline neoadjuvant chemotherapy.
• High SPAG5 transcript and protein concentrations predicted a higher pathological complete response rate to combination chemotherapy.

Conclusions:

• SPAG5 is a novel amplified gene on chromosome 17q11.2 in breast cancer.
• SPAG5 transcript and protein are independent prognostic and predictive biomarkers.
• SPAG5 may serve as a clinical utility biomarker for predicting sensitivity to combination cytotoxic chemotherapy, particularly in ER-negative breast cancer.