283P - Mad2L1 Overexpression Leads to Early Metastasis in Breast Cancer

Abstract

ABSTRACT Aim: Mitotic arrest deficient 2 (MAD2) is an essential spindle assembly checkpoint (SAC) protein. It prevents the onset of anaphase until all chromosomes are properly aligned at the metaphase plate. Its overexpression leads to short survival and chromosomal instability in lung cancer but its significance in breast cancer has not been investigated yet. Methods: We obtained 7 previously published Affymetrix microarray datasets of breast cancer patients. Probes 203362_s and 1554768_a were mapped on MAD2L1 (MAD2 gene) transcripts and chosen for further analysis. We constructed multivariate Cox proportional hazard survival models of gene expression with distant metastasis-free survival (DMFS). The resulting hazard ratios from each dataset were combined in a meta-analysis (random effects model). Results: In total, 2,538 patients were included. High expression of MAD2L1 was associated with shorter DMFS (HR = 1.17, 95% CI 1.03-3.67, p = 0.011) after multivariate adjustment for tumor node, size and grade. Conclusions: This is the first report showing that overexpression of MAD2L1 leads to early metastasis in breast cancer. Since MAD2 is a major gatekeeper of the mitotic mechanism, understanding MAD2L1 pathophysiology could guide the development of new targeted therapies in breast cancer. Disclosure: All authors have declared no conflicts of interest.