Department of Internal Medicine, Respiratory Research Unit, Clinical Research Center, Oulu University Hospital, FI-90029 Oulu, Finland.
Hum Pathol. 2012 Apr;43(4):577-84. doi: 10.1016/j.humpath.2011.05.024. Epub 2011 Sep 23.
Nuclear factor erythroid-derived 2-like 2 (Nrf2) controls the expression of several enzymes that are protective against oxidative stress. We investigated the expression of nuclear factor erythroid-derived 2-like 2, DJ1 (Nrf2 stabilizer), and sulfiredoxin in a large set of lung carcinomas. The cases were analyzed immunohistochemically with antibodies to nuclear factor erythroid-derived 2-like 2, DJ1, and sulfiredoxin with the results being compared with histologic and clinical data. Significant differences were observed in the expression of DJ1 and sulfiredoxin between various types of lung tumors, while expression of nuclear factor erythroid-derived 2-like 2 was more constant. Patients with tumors with cytoplasmic (P = .033) or nuclear (P = .003) DJ1 positivity exhibited worse survival. Separately in squamous cell carcinomas, there was a tendency toward worse survival with both cytoplasmic (P = .013) and nuclear (P = .071) DJ1 positivity. Patients with a strong nuclear factor erythroid-derived 2-like 2 expression in their tumors had worse survival (P = .006). In the Cox regression analysis, nuclear factor erythroid-derived 2-like 2 was an independent prognostic factor (P = .012) along with the T status (P = .008) and DJ1 cytoplasmic positivity (P = .028). Interestingly, smokers and ex-smokers had significantly more sulfiredoxin expression in their tumors (P < .001); and in patients receiving cytostatic drugs or radiation therapy, sulfiredoxin expression predicted a poor prognosis (P = .038). Nuclear factor erythroid-derived 2-like 2 and its stabilizing protein DJ1 affect the prognosis of patients with lung cancer by inducing an elevated stress response to oxidative damage. There were differences in the expression of sulfiredoxin and DJ1 between different lung tumor types, suggesting that the pathways involved in combating oxidative stress vary in different lung cancer types.
核因子红细胞 2 相关因子 2（Nrf2）控制着几种对氧化应激具有保护作用的酶的表达。我们研究了大量肺癌病例中核因子红细胞 2 相关因子 2、DJ1（Nrf2 稳定剂）和硫氧还蛋白的表达。用针对核因子红细胞 2 相关因子 2、DJ1 和硫氧还蛋白的抗体对这些病例进行免疫组织化学分析，并将结果与组织学和临床数据进行比较。在各种类型的肺癌肿瘤中，DJ1 和硫氧还蛋白的表达存在显著差异，而核因子红细胞 2 相关因子 2 的表达则更为稳定。肿瘤细胞质（P =.033）或核（P =.003）DJ1 阳性的患者生存情况较差。在单独的鳞状细胞癌中，细胞质（P =.013）和核（P =.071）DJ1 阳性均有生存较差的趋势。肿瘤中 Nrf2 表达较强的患者生存情况较差（P =.006）。在 Cox 回归分析中，Nrf2 是独立的预后因素（P =.012），与 T 分期（P =.008）和细胞质 DJ1 阳性（P =.028）一样。有趣的是，吸烟者和曾经吸烟者的肿瘤中硫氧还蛋白表达明显增加（P <.001）；接受细胞毒药物或放射治疗的患者中，硫氧还蛋白表达预示预后不良（P =.038）。核因子红细胞 2 相关因子 2 及其稳定蛋白 DJ1 通过诱导对氧化损伤的应激反应来影响肺癌患者的预后。不同类型的肺癌中硫氧还蛋白和 DJ1 的表达存在差异，表明不同类型的肺癌对抗氧化应激的途径不同。
