title: NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix.
abstract: BACKGROUND
  NQO1 (NAD(P)H: quinone oxidoreductase-1), located on chromosome 16q22, functions primarily to protect normal cells from oxidant stress and electrophilic attack. Recent studies have revealed that NQO1 is expressed at a high level in most human solid tumors including those of the colon, breast, pancreas, ovaries and thyroid, and it has also been detected following the induction of cell cycle progression and proliferation of melanoma cells. In this study, we aimed to investigate the clinicopathological significance of upregulated NQO1 protein expression in squamous cell carcinomas (SCCs) of the uterine cervix.
  
  
  METHODS
  The localization of the NQO1 protein was determined in the SiHa cervical squamous cancer cell line using immunofluorescence (IF) staining, and immunohistochemical (IHC) staining performed on paraffin-embedded cervical SCC specimens from 177 patients. For comparison, 94 cervical intraepithelial neoplasia (CIN) and 25 normal cervical epithelia samples were also included. QRT-PCR was performed on RNA from fresh tissues to detect NQO1 mRNA expression levels, and HPV infection status was genotyped using oligonucleotide microarray. Disease-free survival (DFS) and 5-year overall survival (OS) rates for all cervical SCC patients were calculated using the Kaplan-Meier method, and univariate and multivariate analysis was performed using the Cox proportional hazards regression model.
  
  
  RESULTS
  The NQO1 protein showed a mainly cytoplasmic staining pattern in cervical cancer cells, and only three cases of cervical SCC showed a nuclear staining pattern. The strongly positive rate of NQO1 protein expression was significantly higher in cervical SCCs and CINs than in normal cervical epithelia. High-level NQO1 expression was closely associated with poor differentiation, late-stage, lymph node metastasis and high-risk for HPV infection. Additionally, high-level NQO1 expression was associated with lower DFS and 5-year OS rates, particularly for patients with early-stage cervical SCCs. Furthermore, Cox analysis revealed that NQO1 expression emerged as a significant independent hazard factor for DFS rate in patients with cervical SCC.
  
  
  CONCLUSIONS
  NQO1 overexpression might be an independent biomarker for prognostic evaluation of cervical SCCs.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.forename: Jienan
authors.initials: J
authors.lastname: Kong
authors.forename: Guanghai
authors.initials: G
authors.lastname: Yan
authors.forename: Xiangshan
authors.initials: X
authors.lastname: Ren
authors.forename: Dan
authors.initials: D
authors.lastname: Jin
authors.affiliation: Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, China. jintf@ybu.edu.cn.
authors.forename: Tiefeng
authors.initials: T
authors.lastname: Jin
authors.forename: Lijuan
authors.initials: L
authors.lastname: Lin
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Lin
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000821:virology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000096:biosynthesis* / Q000235:genetics; D027383:Papillomaviridae / Q000472:pathogenicity; D011379:Prognosis; D016016:Proportional Hazards Models; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology
chemical_list: D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human