title: AKR1B10 overexpression in breast cancer: association with tumor size, lymph node metastasis and patient survival and its potential as a novel serum marker.
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.
authors.affiliation: Department of Medical Microbiology, Immunology, and Cell Biology, Simmons Cancer Institute, Southern Illinois University School of Medicine, Springfield, IL 62794, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Di-Xian
authors.initials: DX
authors.lastname: Luo
authors.forename: Chenfei
authors.initials: C
authors.lastname: Huang
authors.forename: Yi
authors.initials: Y
authors.lastname: Shen
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Bu
authors.forename: Stephen
authors.initials: S
authors.lastname: Markwell
authors.forename: John
authors.initials: J
authors.lastname: Gao
authors.forename: Jianghua
authors.initials: J
authors.lastname: Liu
authors.forename: Xuyu
authors.initials: X
authors.lastname: Zu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Cao
authors.forename: Zachary
authors.initials: Z
authors.lastname: Gao
authors.forename: Fengmin
authors.initials: F
authors.lastname: Lu
authors.forename: Duan-Fang
authors.initials: DF
authors.lastname: Liao
authors.forename: Deliang
authors.initials: D
authors.lastname: Cao
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000097:blood / Q000502:physiology*; D000074408:Aldo-Keto Reductases; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase