Significance of NQO1 overexpression for prognostic evaluation of gastric adenocarcinoma

Lin, Lijuan; Qin, Yunzhi; Jin, Tiefeng; Liu, Shuangping; Zhang, Songnan; Shen, Xionghu; Lin, Zhenhua

doi:10.1016/j.yexmp.2013.12.008

Cited by 45 publications

(39 citation statements)

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“…Our previous study [24] also showed that NQO1 was a significant prognostic or predictive marker in gastric cancer. In this study, we performed IHC staining and analysis of 177 cervical SCC samples, 94 precancerous disease samples and 25 normal epithelium tissues of the uterine cervix, and found that the strongly positive rate of NQO1 protein expression in both SCCs and CINs was significantly higher than in the normal cervix.…”

Section: Discussionmentioning

confidence: 91%

“…Some studies have shown that the polymorphism in the NQO1 gene affects the translation of the NQO1 protein. The NQO1 C609T polymorphism has been reported to be associated with an increased risk of various cancers such as renal [21], lung [22], esophageal [23], gastric [24] and head and neck [25]. Hu’ results indicated that functional polymorphisms in NQO1 SNP609 associate with the risk of cervical cancer especially in women infected with type 16- and/or type 18-related HPVs [26].…”

Section: Discussionmentioning

confidence: 99%

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

Kong

Yan

et al. 2014

BMC Cancer

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BackgroundNQO1 (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.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.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

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

Kong

Yan

et al. 2014

BMC Cancer

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“…Additionally we are able to tease out an apparent "extensive metabolizer" subset of individuals who we know cannot be polymorphic, which probably represents environmental plasticity in NQO1 in this population. Although the effects of NQO1 slow metabolizer polymorphisms/phenotypes have been extensively studied in the context of susceptibility to cancer and effects on drug metabolism, demonstrating environmental mechanisms for enzyme plasticity in human tissues is far more rare (David et al, 2003;Guha et al, 2008;Goodrich et al, 2009;Han et al, 2009;Martin et al, 2009;Vijayakrishnan and Houlston, 2010;Kolesar et al, 2011;Tsvetkov et al, 2011;Li and Zhou, 2014;Lin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…In the adult population, increased cardiovascular and cancer risks (Han et al, 2009;Martin et al, 2009;Kolesar et al, 2011;Lin et al, 2014) as well as increasing severity of Alzheimer's disease in the elderly have also been linked to NQO1 polymorphisms (Tsvetkov et al, 2011). Given these associations with childhood diseases and diseases of aging, the NQO1 enzyme is understudied with respect to ontogeny.…”

Section: Introductionmentioning

confidence: 99%

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Rougée

Riches

Berman

et al. 2016

Drug Metabolism and Disposition

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The NADPH dehydrogenase quinone oxido-reductase 1 (NQO1) enzyme is an antioxidant and metabolic enzyme that performs two electron reduction of quinones and other chemicals. Based on the physiologic role(s) of NQO1, we hypothesized that expression and activity of this enzyme would vary with age and other demographic variables. Cytosols from 117 archived human livers were investigated for changes in NQO1 with age, sex, obesity, and ethnicity. Protein expression but not activity of NQO1 was weakly negatively correlated with age (Spearman r = -0.2, P = 0.03). No sex differences were observed for either protein expression or activity and for ethnicity; Caucasians had greater NQO1 activity than Asians (P < 0.05). Overweight children had statistically significantly higher NQO1 activity as compared with ideal weight children (P < 0.05) although this difference was not observed in adults. These findings establish that NQO1 is approximately as active in children as adults. However, modeled NQO1 clearance (both allometric and physiologically based pharmacokinetics) predicted maturation at 23 to 26 years. This is almost certainly an overestimate, with error in the model resulting from a small sample size and inability to scale for age-related changes in hepatic cellularity and/or cytosolic protein content, and indicates a delay in reaching maximum clearance through the NQO1 pathway that is affected by physiologic development as much, or more than, biochemical development. Obesity may increase hepatic NQO1 activity in children, which is likely a protective mechanism in oxidative stress, but may also have significant implications for drug and chemical disposition in obese children.

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“…The exact function of NQO1 in cancer genesis is not yet determined, but it is known that it activates the apoptotic protein TP53 and it is a priority target of glioblastoma chemotherapy [52, 53]. …”

Section: Discussionmentioning

confidence: 99%

Combination of unsaturated fatty acids and ionizing radiation on human glioma cells: cellular, biochemical and gene expression analysis

Antal

Hackler²,

Shen

et al. 2014

Lipids Health Dis

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BackgroundBased on previous observations a potential resort in the therapy of the particularly radioresistant glioma would be its treatment with unsaturated fatty acids (UFAs) combined with irradiation.MethodsWe evaluated the effect of different UFAs (arachidonic acid (AA), docosahexaenoic acid (DHA), gamma-linolenic acid (GLA), eicosapentaenoic acid (EPA) and oleic acid (OA)) on human U87 MG glioma cell line by classical biochemical end-point assays, impedance-based, real-time cellular and holographic microscopic analysis. We further analyzed AA, DHA, and GLA at morphological, gene and miRNA expression level.ResultsCorresponding to LDH-, MTS assays and real-time cytoxicity profiles AA, DHA, and GLA enhanced the radio sensitivity of glioma cells. The collective application of polyunsaturated fatty acids (PUFAs) and irradiation significantly changed the expression of EGR1, TNF-α, NOTCH1, c-MYC, TP53, HMOX1, AKR1C1, NQO1, while up-regulation of GADD45A, EGR1, GRP78, DDIT3, c-MYC, FOSL1 were recorded both in response to PUFA treatment or irradiation alone. Among the analyzed miRNAs miR-146 and miR-181a were induced by DHA treatment. Overexpression of miR-146 was also detected by combined treatment of GLA and irradiation.ConclusionsBecause PUFAs increased the radio responsiveness of glioma cells as assessed by biochemical and cellular assays, they might increase the therapeutic efficacy of radiation in treatment of gliomas. We demonstrated that treatment with DHA, AA and GLA as adjunct to irradiation up-regulated the expression of oxidative-stress and endoplasmic reticulum stress related genes, and affected NOTCH1 expression, which could explain their additive effects.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-511X-13-142) contains supplementary material, which is available to authorized users.

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Significance of NQO1 overexpression for prognostic evaluation of gastric adenocarcinoma

Cited by 45 publications

References 14 publications

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

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

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Combination of unsaturated fatty acids and ionizing radiation on human glioma cells: cellular, biochemical and gene expression analysis

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