Abstract
Background: Platinum-based therapy is an effective treatment for a subset of triple-negative breast cancer and ovarian cancer patients. In order to increase response rate and decrease unnecessary use, robust biomarkers that predict response to therapy are needed. Patients and methods: We performed an integrated genomic approach combining differential analysis of gene expression and DNA copy number in sensitive compared with resistant triple-negative breast cancers in two independent neoadjuvant cisplatin-treated cohorts. Functional relevance of significant hits was investigated in vitro by overexpression, knockdown and targeted inhibitor treatment. Results: We identified two genes, the Bloom helicase (BLM) and Fanconi anemia complementation group I (FANCI), that have both increased DNA copy number and gene expression in the platinum-sensitive cases. Increased level of expression of these two genes was also associated with platinum but not with taxane response in ovarian cancer. As a functional validation, we found that overexpression of BLM promotes DNA damage and induces sensitivity to cisplatin but has no effect on paclitaxel sensitivity. Conclusions: A biomarker based on the expression levels of the BLM and FANCI genes is a potential predictor of platinum sensitivity in triple-negative breast cancer and ovarian cancer.
Original language | English (US) |
---|---|
Pages (from-to) | 903-909 |
Number of pages | 7 |
Journal | Annals of Oncology |
Volume | 29 |
Issue number | 4 |
DOIs | |
State | Published - Apr 1 2018 |
Externally published | Yes |
Keywords
- Gene expression-based predictor of treatment sensitivity
- Ovarian cancer
- Platinum-based chemotherapy
- Triple-negative breast cancer
ASJC Scopus subject areas
- Hematology
- Oncology