NQO1 overexpression is associated with poor prognosis in squamous cell carcinoma of the uterine cervix

BMC Cancer

Yue Ma²  Jienan Kong²  Guanghai Yan³  Xiangshan Ren²  Dan Jin¹  Tiefeng Jin²  Lijuan Lin⁴  Zhenhua Lin² 

[1] Department of Internal Medicine, Yanji City Hospital, Yanji, China

[2] Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji, China

[3] Department of Anatomy and Histology and Embryology, Yanbian University Medical College, Yanji, China

[4] Department of Medical Imaging, College of Medicine, Eastern Liaoning University, Dandong, China

关键词: Survival analysis;    Prognosis;    Human papillomavirus;    NQO1;    Cervix uteri;    Squamous cell carcinoma;   

Others  :  1125389
DOI  :  10.1186/1471-2407-14-414

 received in 2014-01-13, accepted in 2014-05-16,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Ma et al.; licensee BioMed Central Ltd.

【 图 表 】

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