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BMC Cancer

, 14:414

Genetics, genomics and epigenetics

Abstract

BackgroundNQO1 NADPH: 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.

MethodsThe 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.

ResultsThe 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.

ConclusionsNQO1 overexpression might be an independent biomarker for prognostic evaluation of cervical SCCs.

KeywordsSquamous cell carcinoma Cervix uteri NQO1 Human papillomavirus Prognosis Survival analysis Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-414 contains supplementary material, which is available to authorized users.

Yue Ma, Jienan Kong contributed equally to this work.

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Autor: Yue Ma - Jienan Kong - Guanghai Yan - Xiangshan Ren - Dan Jin - Tiefeng Jin - Lijuan Lin - Zhenhua Lin

Fuente: https://link.springer.com/



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