Abstract
BackgroundNAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein that catalyzes two-electron reduction and detoxification of quinones and its derivatives. NQO1 catalyzes reactions that have a protective effect against redox cycling, oxidative stress and neoplasia. High expression of NQO1 is associated with many solid tumors including those affecting the colon, breast and pancreas; however, its role in the progression of ovarian carcinoma is largely undefined. This study aimed to investigate the clinicopathological significance of high NQO1 expression in serous ovarian carcinoma.MethodsNQO1 protein expression was assessed using immunohistochemical (IHC) staining in 160 patients with serous ovarian carcinoma, 62 patients with ovarian borderline tumors and 53 patients with benign ovarian tumors. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect NQO1 mRNA expression levels. The correlation between high NQO1 expression and clinicopathological features of ovarian carcinoma was evaluated by Chi-square and Fisher’s exact test. Overall survival (OS) rates of all of ovarian carcinoma patients were calculated using the Kaplan-Meier method, and univariate and multivariate analyses were performed using the Cox proportional hazards regression model.ResultsNQO1 protein expression in ovarian carcinoma cells was predominantly cytoplasmic. Strong, positive expression of NQO1 protein was observed in 63.8% (102/160) of ovarian carcinomas, which was significantly higher than in borderline serous tumors (32.3%, 20/62) or benign serous tumors (11.3%, 6/53). Importantly, the rate of strong, positive NQO1 expression in borderline serous tumors was also higher than in benign serous tumors. High expression of NQO1 protein was closely associated with higher histological grade, advanced clinical stage and lower OS rates in ovarian carcinomas. Moreover, multivariate analysis indicated that NQO1 was a significant independent prognostic factor, in addition to clinical stage, in patients with ovarian carcinoma.ConclusionsNQO1 is frequently upregulated in ovarian carcinoma. High expressin of NQO1 protein may be an effective biomarker for poor prognostic evaluation of patients with serous ovarian carcinomas.
Highlights
NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein that catalyzes two-electron reduction and detoxification of quinones and its derivatives
The rates of positive and strongly positive NAD(P)H:quinone oxidoreductase 1 (NQO1) protein expression in borderline serous tumors were significantly higher than in benign serous tumors (P < 0.05) (Table 1). In keeping with these results, analysis of NQO1 mRNA levels by Quantitative real-time polymerase chain reaction (qRT-PCR) confirmed elevated levels of NQO1 transcript in serous ovarian carcinoma samples compared with benign ovarian tumors in fresh tissues (Figure 2)
Correlation between NQO1 expression status and clinicopathological features of serous ovarian carcinoma To evaluate the relationship between NQO1 protein and ovarian carcinoma progression, we analyzed the correlation between high NQO1 expression and clinicopathological features of ovarian carcinomas
Summary
NAD(P)H:quinone oxidoreductase (NQO1) is a flavoprotein that catalyzes two-electron reduction and detoxification of quinones and its derivatives. NQO1 provides cells with multiple layers of protection against oxidative stress, including the direct detoxification of highly reactive quinones, the maintenance of lipid-soluble antioxidants in reduced forms, and stabilization of the tumor suppressor p53 [6]. Increasing evidence suggests that high expression of NQO1 at the early stages of carcinogenesis may provide cancer cells with a growth advantage [7,8,9]. Certain quinones, such as mitomycin C, streptonigrin, E09 and RH1, are bioactivated by NQO1 [10,11,12,13,14]. To date, the role of NQO1 in ovarian carcinoma progression remains unclear
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