Myxovirus resistance 1 (MX1) is an independent predictor of poor outcome in invasive breast cancer

Abstract

Background Breast cancer (BC) is a disease with variable morphology, clinical behaviour and response to therapy. Identifying factors associated with the progression of early-stage BC can help understand the risk of metastasis and guide treatment decisions. Myxovirus resistance 1 (MX1), which is involved in the cellular antiviral mechanism, plays a role in some solid tumours; however, its role in invasive BC remains unknown. In this study, we aimed to explore the clinicopathological and prognostic significance of MX1 in BC. Methods MX1 was assessed at the protein level using tissue microarrays from a large well-annotated BC cohort (n = 845). The expression of MX1 mRNA was assessed at the transcriptomic level using the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC; n = 1980) and validated using three publicly available cohorts on Breast Cancer Gene-Expression Miner (bc-GenExMiner version 4.4). The associations between MX1 expression and clinicopathological factors, and outcome were evaluated. Results High MX1 protein expression was associated with features of aggressiveness, including large tumour size, high tumour grade, high Nottingham prognostic index scores, hormone receptor negativity and high Ki67 expression. High MX1 expression showed an association with poor patient outcome and it was an independent predictor of short BC-specific survival (p = 0.028; HR = 1.5; 95% CI = 1.0–2.2). Consistent with the protein results, high MX1 mRNA levels showed an association with features of aggressive behaviour and with shorter survival. Conclusion This study identified MX1 as an independent predictor of poor outcome in patients with BC. Further functional studies are needed to investigate the biological role of MX1 in BC and its potential value as a therapeutic target.

Inhibition of interferon-signalling halts cancer-associated fibroblast-dependent protection of breast cancer cells from chemotherapy

“…Our data tie together previous reports showing that CAFs are associated with poor outcomes in TNBC patients, 8 that breast CAFs can secrete IFNβ thereby activating IFN signalling and influencing behaviour of breast cancer cells in vitro, 32 , 33 and that expression of MX1 in breast cancer cells is significantly associated with poor outcomes in patients. 34 Critically, we define the functional impact of this signalling on cancer cells in terms of chemotherapy resistance (Figs. 1 and 4 ), and indeed chemotherapy-treatment itself contributes to induction of full paracrine activity (Figs.…”

ANGPTL4 overexpression is associated with progression and poor prognosis in breast cancer

“…Although there has been a rapid development of therapeutic modalities that resulted in a ~38% decreased mortality rate, patients with metastasis and local recurrence continue having a poor prognosis (3). The degree of malignancy, prognosis and treatment failure is associated with numerous factors, including the existence of stem cells, GTPases and angiogenesis (4)(5)(6). Angiopoietin-like 4 (ANGPTL4) is a protein belonging to the ANGPTL family that was discovered in 2000 (7,8).…”

Genomic analyses identify biological processes in ZKSCAN3-deficient colorectal cancer cells

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