Increased expression of Mitotic Arrest Deficient-Like 1 (MAD1L1) is associated with poor prognosis and insensitive to Taxol treatment in breast cancer

• DOI: 10.1007/s10549-013-2633-8
• Publication Date: 2013-07-16T07:17:38Z
• Authors: Qian Sun; Xianyu Zhang; Tong Liu; Xiaolong Liu; Jingshu Geng; Xiaohui He; Yang Liu; Da Pang
• Keywords: Adult; 0301 basic medicine; 0303 health sciences; Paclitaxel; Nuclear Proteins; Breast Neoplasms; Cell Cycle Proteins; Middle Aged; Prognosis; 3. Good health; Gene Expression Regulation, Neoplastic; 03 medical and health sciences; Tissue Array Analysis; Chromosomal Instability; Biomarkers, Tumor; Humans; Female; Aged

Aneuploidy is a characteristic of human cancers, and recent studies have suggested that defects of mitotic checkpoints play a role in carcinogenesis. Mitotic Arrest Deficient-Like 1 (MAD1L1), whose altered expression is associated with chromosomal instability, is a checkpoint gene. We examined MAD1L1 protein expression from 461 breast cancer tissues and patients' normal breast tissues by tissue microarray to study the correlation between the MAD1L1 expression and the clinicopathological features. MAD1L1 protein expression was significantly increased in the nuclei of cancer cells (28.4 %) compared with that in normal mammary cells (2.2 %), and was correlated with Her-2 status, cancer subtypes, p53 status, and age. High level of MAD1L1 expression in nuclei was associated with worse OS (p = 0.018). Furthermore, patients with high level of MAD1L1 expression (in nuclei) and undergone Taxol chemotherapy treatment have shorter overall survival than ones without Taxol treatment in this study (p = 0.026). In conclusion, our data demonstrated a significant correlation between nuclear expression of MAD1L1 protein and adverse prognosis in breast cancer. MAD1L1 might be used as a prognostic biomarker for breast cancer and expression of MAD1L1 in nuclei is also a predict biomarker of contraindication to pacilitaxel treatment in breast cancer.