Investigating type I interferon gene signatures in breast cancer patients (#298)
Bone metastasis is a key characteristic of end-stage breast cancer and severely reduces patient survival. While staging and grading of primary tumour cells help to characterise the invasive nature of the tumour, currently there is no way of definitely predicting prognosis in breast cancer patients. Interferon regulatory factor 7 (IRF7) is a transcription factor known to be a key regulator of type I IFN. We recently showed that the loss of IRF7 expression in bone metastases compared to primary breast tumour cells results in reduced type I IFN activation of peripheral anti-tumour immunity; thus enabling metastasis1. The aim of this project is to investigate the type I IFN-regulated gene expression in human peripheral blood and whether a signature exists in breast cancer patients as a potential marker for prognosis. Transcription profiling microarray experiments will be performed using peripheral blood mononuclear cells (PBMC) from healthy donors; breast cancer patients who responded to chemotherapy; and non-responders. The gene signature derived in the previous aim will be refined using Interferome v2.02 and 'Enrich' and used to examine whether the type I IFN-regulated gene signature is expressed differentially as a reflection of the presence or absence of an intact IFN/IRF7 pathway in primary breast cancer cells and further, whether differential expression indicates prognosis.
- Bidwell BN, Slaney CY, Withana NP, Forster S, Cao Y, Loi S, et al. Silencing of Irf7 pathways in breast cancer cells promotes bone metastasis through immune escape. Nat Med. 2012;18(8):1224-31.
- Rusinova I, Forster S, Yu S, Kannan A, Masse M, Cumming H, et al. Interferome v2.0: an updated database of annotated interferon-regulated genes. Nucleic Acids Res. 2013;41(Database issue):D1040-6.