AKR1B10 overexpression in breast cancer: association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker |
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Authors: | Ma Jun Luo Di-Xian Huang Chenfei Shen Yi Bu Yiwen Markwell Stephen Gao John Liu Jianghua Zu Xuyu Cao Zhe Gao Zachary Lu Fengmin Liao Duan-Fang Cao Deliang |
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Institution: | Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA. |
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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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Keywords: | aldo‐keto reductase 1B10 breast cancer disease‐related survival prognostic marker serum marker |
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