title: Prognostic significance of minichromosome maintenance proteins in breast cancer.
abstract: A role for the minichromosome maintenance (MCM) proteins in cancer initiation and progression is slowly emerging. Functioning as a complex to ensure a single chromosomal replication per cell cycle, the six family members have been implicated in several neoplastic disease states, including breast cancer. Our study aim to investigate the prognostic significance of these proteins in breast cancer. We studied the expression of MCMs in various datasets and the associations of the expression with clinicopathological parameters. When considered alone, high level MCM4 overexpression was only weakly associated with shorter survival in the combined breast cancer patient cohort (n = 1441, Hazard Ratio = 1.31; 95% Confidence Interval = 1.11-1.55; p = 0.001). On the other hand, when we studied all six components of the MCM complex, we found that overexpression of all MCMs was strongly associated with shorter survival in the same cohort (n = 1441, Hazard Ratio = 1.75; 95% Confidence Interval = 1.31-2.34; p < 0.001), suggesting these MCM proteins may cooperate to promote breast cancer progression. Indeed, their expressions were significantly correlated with each other in these cohorts. In addition, we found that increasing number of overexpressed MCMs was associated with negative ER status as well as treatment response. Together, our findings are reproducible in seven independent breast cancer cohorts, with 1441 patients, and suggest that MCM profiling could potentially be used to predict response to treatment and prognosis in breast cancer patients.
authors: Faculty of Health Sciences, University of Macau, Avenida de Universidade Macau, China ; CRUK Cambridge Institute, University of Cambridge United Kingdom CB2 0RE ; Center for Cancer Research and Cell Biology (CCRCB) and School of Pharmacy, Queen's University Belfast United Kingdom BT9 7BL.
authors: Hang Fai
authors: HF
authors: Kwok
authors: Center for Cancer Research and Cell Biology (CCRCB) and School of Pharmacy, Queen's University Belfast United Kingdom BT9 7BL.
authors: Shu-Dong
authors: SD
authors: Zhang
authors: Center for Cancer Research and Cell Biology (CCRCB) and School of Pharmacy, Queen's University Belfast United Kingdom BT9 7BL.
authors: Cian M
authors: CM
authors: McCrudden
authors: Institute of Molecular and Cell Biology, ASTAR Singapore ; Center for Cancer Research and Cell Biology (CCRCB) and School of Pharmacy, Queen's University Belfast United Kingdom BT9 7BL.
authors: Hiu-Fung
authors: HF
authors: Yuen
authors: Department of Pathology and Obsterics & Gyneecology, University of Hong Kong Hong Kong, China.
authors: Kam-Po
authors: KP
authors: Ting
authors: Center for Cancer Research and Cell Biology (CCRCB) and School of Pharmacy, Queen's University Belfast United Kingdom BT9 7BL.
authors: Qing
authors: Q
authors: Wen
authors: Department of Pathology and Obsterics & Gyneecology, University of Hong Kong Hong Kong, China.
authors: Ui-Soon
authors: US
authors: Khoo
authors: Department of Pathology and Obsterics & Gyneecology, University of Hong Kong Hong Kong, China.
authors: Kelvin Yuen-Kwong
authors: KY
authors: Chan
keywords: Minichromosome maintenance complex; breast cancer; prognosis; survival
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