Hubackova Miluse, Vaclavikova Radka, Mrhalova Marcela, Kubackova Katerina, Kodet Roman, Gut Ivan, Soucek Pavel
Laboratory of Toxicogenomics, National Institute of Public Health, Prague, Czech Republic.
Pharmacogenet Genomics. 2009 Jul;19(7):505-12. doi: 10.1097/FPC.0b013e32832cf9cf.
The aim of this study was to further clarify the recently reported role of NAD(P)H:quinone oxidoreductase 1 (NQO1) as a strong prognostic and predictive factor in breast cancer.
NQO1 transcript levels were monitored in mammary tumors by real-time polymerase chain reaction. NQO1 protein levels were immunohistochemically determined in formalin-fixed paraffin-embedded tissues. NQO1 polymorphism (Pro187Ser, rs1800566) was also assessed. Evaluation (N=52) and validation (N=53) sets were analyzed subsequently.
Carriers of variant NQO1-Ser allele had significantly more frequently NQO1-negative protein expression (P=0.001) in both sets. NQO1 transcript levels in samples with negative protein expression were significantly lower than in those with positive NQO1 protein expression (P=0.007) in both sets. Patients with stages 0/I/II had more often positive NQO1 protein expression than patients with stages III/IV (P=0.022) in the evaluation set. Significant association between NQO1 protein expression and TP53 protein status was also found (P=0.037). However, both associations were not replicated by analysis of the validation set. Analysis of both sets combined did not show significant association of NQO1 protein expression either with stage (P=0.231) or with TP53 protein status (P>0.999). Thus, the results observed in the evaluation set were effects of small sample size.
The role of NQO1 in human mammary gland carcinogenesis does not seem to be directly associated with classical clinico-pathological factors.
本研究旨在进一步阐明近期报道的NAD(P)H：醌氧化还原酶1（NQO1）作为乳腺癌重要预后和预测因子的作用。
通过实时聚合酶链反应监测乳腺肿瘤中NQO1转录水平。在福尔马林固定石蜡包埋组织中通过免疫组织化学测定NQO1蛋白水平。还评估了NQO1基因多态性（Pro187Ser，rs1800566）。随后分析评估集（N = 52）和验证集（N = 53）。
在两个数据集中，NQO1-Ser变异等位基因携带者的NQO1蛋白阴性表达频率均显著更高（P = 0.001）。在两个数据集中，蛋白表达阴性的样本中NQO1转录水平均显著低于NQO1蛋白表达阳性的样本（P = 0.007）。在评估集中，0/I/II期患者的NQO1蛋白阳性表达频率高于III/IV期患者（P = 0.022）。还发现NQO1蛋白表达与TP53蛋白状态之间存在显著关联（P = 0.037）。然而，验证集分析未重复这两种关联。对两个数据集合并分析未显示NQO1蛋白表达与分期（P = 0.231）或TP53蛋白状态（P>0.999）之间存在显著关联。因此，评估集中观察到的结果是小样本量的影响。
NQO1在人类乳腺致癌过程中的作用似乎与经典临床病理因素无直接关联。
