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.
Yang
Y
Yang
Yan
Y
Zhang
Qunying
Q
Wu
Xuelian
X
Cui
Zhenhua
Z
Lin
Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China. liushp@ybu.edu.cn.
Shuangping
S
Liu
Liyan
L
Chen
D001943:Breast Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000401:mortality / Q000556:secondary; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D061986:MCF-7 Cells; D008875:Middle Aged; D015999:Multivariate Analysis; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D016016:Proportional Hazards Models; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism
D016660:NAD(P)H Dehydrogenase (Quinone); D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; C447479:NQO1 protein, human; C508053:ERBB2 protein, human