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MAD1L1 表达增加与乳腺癌不良预后相关,并对紫杉醇治疗不敏感。

Increased expression of mitotic arrest deficient-like 1 (MAD1L1) is associated with poor prognosis and insensitive to Taxol treatment in breast cancer.

机构信息

Department of Breast Surgery, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, China.

出版信息

Breast Cancer Res Treat. 2013 Jul;140(2):323-30. doi: 10.1007/s10549-013-2633-8. Epub 2013 Jul 17.

DOI:10.1007/s10549-013-2633-8
PMID:23860928
Abstract

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.

摘要

非整倍体是人类癌症的特征,最近的研究表明,有丝分裂检查点的缺陷在致癌作用中起作用。有丝分裂阻滞缺陷样 1(MAD1L1),其表达改变与染色体不稳定性相关,是一个检查点基因。我们通过组织微阵列检查了 461 例乳腺癌组织和患者正常乳腺组织中的 MAD1L1 蛋白表达,以研究 MAD1L1 表达与临床病理特征之间的相关性。与正常乳腺细胞(2.2%)相比,癌细胞核中的 MAD1L1 蛋白表达明显增加(28.4%),并与 Her-2 状态、癌症亚型、p53 状态和年龄相关。核中 MAD1L1 高表达与 OS 较差相关(p=0.018)。此外,在这项研究中,与未接受紫杉醇治疗的患者相比,核中 MAD1L1 高表达(核)且接受紫杉醇化疗的患者的总生存期更短(p=0.026)。总之,我们的数据表明,MAD1L1 蛋白的核表达与乳腺癌的不良预后显著相关。MAD1L1 可能作为乳腺癌的预后生物标志物,核中 MAD1L1 的表达也是乳腺癌对紫杉醇治疗禁忌的预测生物标志物。

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