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AKR1B10 overexpression in breast cancer: Association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker
Author(s) -
Ma Jun,
Luo DiXian,
Huang Chenfei,
Shen Yi,
Bu Yiwen,
Markwell Stephen,
Gao John,
Liu Jianghua,
Zu Xuyu,
Cao Zhe,
Gao Zachary,
Lu Fengmin,
Liao DuanFang,
Cao Deliang
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27618
Subject(s) - breast cancer , medicine , carcinogenesis , cancer , metastasis , lymph node , breast disease , ca 15 3 , mammary gland , ca15 3 , oncology , univariate analysis , pathology , cancer research , multivariate analysis
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.