Downregulation of Matrix Gla Protein Is A Biomarker for Tamoxifen-Resistant and Radioresistant Breast Cancer

Abstract

Aim: To establish downregulated biomarkers for cross-resistance for radiotherapy (RT) in tamoxifen (TAM)-resistant breast cancer cells. Materials & methods: RNA sequencing was performed on TAM and RT-resistant breast cancer cells. Breast cancer patient cohorts were queried in silico for associations between genes of interest and outcome after TAM treatment or irradiation. Results: 20 genes showed decreased expression in both TAM-resistant and RT-resistant breast cancer cells. Only matrix Gla protein in the primary tumor was associated with outcome after TAM treatment or RT in breast cancer patients. Conclusion: Matrix Gla protein is a biomarker for therapy sensitivity in breast cancer.

Keywords:

• irradiation
• matrix Gla-protein
• radiotherapy
• tamoxifen treatment
• treatment resistance

Author contributions

AEM Post designed the study, developed methodology, acquired, analyzed and interpreted the data, and wrote the manuscript. J Bussink designed the study, interpreted the data, reviewed and revised the manuscript, and supervised the study. M Smid analyzed the data and reviewed the manuscript. FCGJ Sweep designed the study, interpreted the data, reviewed and revised the manuscript, and supervised the study. PN Span designed the study, developed methodology, acquired, analyzed and interpreted the data, reviewed and revised the manuscript, and supervised the study.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Availability of data & materials

The datasets used during the current study are available from the corresponding author on request.