AKR1B10 overexpression in breast cancer: Association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker*

Authors

  • Jun Ma,

    1. Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794
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    • *

      J.M. and D.-X.L. contributed equally to this work

  • Di-Xian Luo,

    1. Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794
    2. Institute of Translational Medicine, the First People's Hospital of Chenzhou, Chenzhou 423000, China
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    • *

      J.M. and D.-X.L. contributed equally to this work

  • Chenfei Huang,

    1. Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794
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  • Yi Shen,

    1. Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794
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  • Yiwen Bu,

    1. Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794
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  • Stephen Markwell,

    1. Division of Statistics and Research Consulting, Southern Illinois University School of Medicine, Springfield, IL 62794
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  • John Gao,

    1. Department of Pathology, Memorial Medical Center, Springfield, IL 62702
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  • Jianghua Liu,

    1. The First Affiliated Hospital, University of South China, Hengyang 421001 China
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  • Xuyu Zu,

    1. The First Affiliated Hospital, University of South China, Hengyang 421001 China
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  • Zhe Cao,

    1. Institute of Pharmacy and Pharmacology, College of Pharmacy and Life Science, University of South China, Hengyang 421001, China
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  • Zachary Gao,

    1. Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794
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  • Fengmin Lu,

    1. Department of Microbiology and Infectious Disease Center, Peking University Health Science Center, Beijing 100083, China
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  • Duan-Fang Liao,

    1. Institute of Pharmacy and Pharmacology, College of Pharmacy and Life Science, University of South China, Hengyang 421001, China
    2. Department of Traditional Chinese Diagnostics, School of Pharmacy, Hunan University of Chinese Medicine, Changsha 420108, China
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  • Deliang Cao

    Corresponding author
    1. Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794
    • Department of Medical Microbiology, Immunology and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine. 913 N. Rutledge Street, Springfield, IL 62794, USA
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    • Tel.: 217-545-9703, Fax. +217-545-3227


Abstract

Aldo-keto reductase 1B10 (AKR1B10) is a secretory protein that is upregulated with tumorigenic transformation of human mammary epithelial cells. This study demonstrated that AKR1B10 was overexpressed in 20 (71.4%) of 28 ductal carcinomas in situ, 184 (83.6%) of 220 infiltrating carcinomas and 28 (87.5%) of 32 recurrent tumors. AKR1B10 expression in breast cancer was correlated positively with tumor size (p = 0.0012) and lymph node metastasis (p = 0.0123) but inversely with disease-related survival (p = 0.0120). Univariate (p = 0.0077) and multivariate (p = 0.0192) analyses both suggested that AKR1B10, alone or together with tumor size and node status, is a significant prognostic factor for breast cancer. Silencing of AKR1B10 in BT-20 human breast cancer cells inhibited cell growth in culture and tumorigenesis in female nude mice. Importantly, AKR1B10 in the serum of breast cancer patients was significantly increased to 15.18 ± 9.08 ng/ml [n = 50; 95% confidence interval (CI), 12.60–17.76], with a high level up to 58.4 ng/ml, compared to 3.34 ± 2.27 ng/ml in healthy donors (n = 60; 95% CI, 2.78–3.90). In these patients, AKR1B10 levels in serum were correlated with its expression in tumors (r = 0.8066; p < 0.0001). Together our data suggests that AKR1B10 is overexpressed in breast cancer and may be a novel prognostic factor and serum marker for this deadly disease.

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