Clinical implications of high NQO1 expression in breast cancers

Background: nad (p) h: quinone oxidoreductase 1 (nqo1) is a xenobiotic metabolizing enzyme that detoxifies chemical stressors and antioxidants,providing cytoprotection in normal tissues. however,high-level expression of nqo1 has been correlated with numerous human malignancies,suggesting a role in carcinogenesis and tumor progression. this study aimed to explore the clinicopathological significance of nqo1 and as a prognostic determinant in breast cancer. methods. a total of 176 breast cancer patients with strict follow-up,45 ductal carcinoma in situ (dcis),22 hyperplasia and 52 adjacent non-tumor breast tissues were selected for immunohistochemical staining of nqo1 protein. immunofluorescence staining was also performed to detect the subcellular localization of nqo1 protein in mcf-7 breast cancer cells. eight fresh breast cancers paired with adjacent non-tumor tissues were quantified using real time rt-pcr (qrt-pcr) and western blot. the correlations between nqo1 overexpression and the clinical features of breast cancer were evaluated using chi-square test and fisher's exact tests. the survival rate was calculated using the kaplan-meier method,and the relationship between prognostic factors and patient survival was also analyzed by the cox proportional hazards models. results: nqo1 protein showed a mainly cytoplasmic staining pattern in breast cancer. the strongly positive rate of nqo1 protein was 61.9% (109/176) in breast cancer,and was significantly higher than in dcis (31.1%,14/45),hyperplasia tissues (13.6%,3/22) and adjacent non-tumor tissues (13.5%,7/52). high-level expression of nqo1 protein was correlated with late clinical stage,poor differentiation,lymph node metastasis,her2 expression and disease-free and 10-year overall survival rates in breast cancer. moreover,multivariate analysis suggested that nqo1 emerged as a significant independent prognostic factor along with clinical stage and her2 expression status in patients with breast cancer. conclusions: high-level expression of nqo1 appears to be associated with breast cancer progression,and may be a potential biomarker for poor prognostic evaluation of breast cancers. © 2014 yang et al.; licensee biomed central ltd.