Division of Clinical Oncology, School of Molecular Medical Sciences, University of Nottingham, Nottingham University Hospitals NHS Trust, Nottingham, UK.
Free Radic Biol Med. 2010 Nov 1;49(8):1263-72. doi: 10.1016/j.freeradbiomed.2010.07.008. Epub 2010 Jul 30.
Ovarian cancer is primarily treated with platinum-based chemotherapy, with ROS generation implicated in cytotoxicity. We examined redox protein expression in ovarian tumors, focusing on the thioredoxin system, to determine the role it might play in mediating response to therapy. Nuclear and cytoplasmic expression of thioredoxin, thioredoxin reductase, thioredoxin-interacting protein, metallothionein, and glutathione S-transferase Pi was assessed, using standard immunohistochemical techniques, on a tissue microarray of 154 primary ovarian carcinomas obtained from patients subsequently treated with adjuvant platinum-based chemotherapy. Low cytoplasmic expression of thioredoxin (p=0.032) and negative nuclear expression of metallothionein (p=0.04) significantly correlated with better progression-free survival. When nuclear and cytoplasmic expression patterns were combined those patients with tumors with low cytoplasmic but high nuclear expression of thioredoxin exhibited better progression-free (p=0.003) and overall survival (p=0.004). This combination was, using multivariate analysis, an independent predictive factor for overall survival (p=0.034). Improved progression-free survival was also seen with negative expression of metallothionein, cytoplasmic and nuclear (p=0.038), and was independent of other clinical parameters (p=0.048). Such results support the suitability of using redox protein expression to predict response and, potentially, to alter treatment options accordingly.
卵巢癌主要采用铂类化疗治疗，活性氧簇的产生与细胞毒性有关。我们研究了卵巢肿瘤中的氧化还原蛋白表达，重点是硫氧还蛋白系统，以确定其在介导对治疗的反应中可能发挥的作用。使用标准免疫组织化学技术，对从随后接受辅助铂类化疗的患者中获得的 154 例原发性卵巢癌的组织微阵列进行了硫氧还蛋白、硫氧还蛋白还原酶、硫氧还蛋白相互作用蛋白、金属硫蛋白和谷胱甘肽 S-转移酶 Pi 的核和细胞质表达评估。低细胞质硫氧还蛋白表达（p=0.032）和阴性核金属硫蛋白表达（p=0.04）与无进展生存期显著相关。当核和细胞质表达模式结合时，那些肿瘤具有低细胞质但高核硫氧还蛋白表达的患者表现出更好的无进展生存期（p=0.003）和总生存期（p=0.004）。这种组合在多变量分析中是总生存期的独立预测因素（p=0.034）。阴性表达金属硫蛋白（p=0.038）和细胞质和核（p=0.038）也观察到无进展生存期的改善，并且独立于其他临床参数（p=0.048）。这些结果支持使用氧化还原蛋白表达来预测反应的适用性，并可能相应地改变治疗选择。
