Prognostic significance of minichromosome maintenance proteins in breast cancer.

Hang Fai Kwok*, Shu-Dong Zhang*, Cian M McCrudden, Hiu-Fung Yuen, Kam-Po Ting, Qing Wen, Ui-Soon Khoo, Kelvin Yuen-Kwong Chan

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    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.
    Original languageEnglish
    Pages (from-to)52-71
    JournalAmerican Journal of Cancer Research
    Volume5
    Issue number1
    Publication statusPublished - 1 Jan 2015

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    Keywords

    • Minichromosome maintenance complex
    • breast cancer
    • survival
    • prognosis

    Cite this

    Kwok*, H. F., Zhang*, S-D., McCrudden, C. M., Yuen, H-F., Ting, K-P., Wen, Q., ... Chan, K. Y-K. (2015). Prognostic significance of minichromosome maintenance proteins in breast cancer. American Journal of Cancer Research, 5(1), 52-71.