Expression Patterns of Nrf2 and Keap1 in Ovarian Cancer Cells and their Prognostic Role in Disease Recurrence and Patient Survival
Expression Patterns of Nrf2 and Keap1 in Ovarian Cancer Cells and their Prognostic Role in Disease Recurrence and Patient Survival
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DOI：
10.1097/igc.0000000000000908
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发表时间：
2017-03-01
影响因子：
4.8
通讯作者：
No, Jae Hong
中科院分区：
文献类型：
--
作者：
Cho, Hye-yon;Kim, Kidong;No, Jae Hong
目的：本研究旨在探讨核因子红细胞2相关因子2（Nrf 2）和Kelch-like ECH相关蛋白1（Keap 1）在卵巢癌中的表达及其作为预后指标的临床价值。分析Nrf 2和Keap 1表达与患者临床病理特征的关系。所有患者均接受含铂化疗。化疗耐药被定义为6个月内复发的一线chemotherapy.Results：观察到在95%和72%，分别在所有100上皮性卵巢癌检查的Nrf 2和Keap 1的胞浆表达。Keap 1低表达（强度= 1）强烈预测更好的总生存期（P = 0.049）和无病生存期（P = 0.004）。考克斯回归分析显示Keap 1表达是影响总生存期的独立预后因素（P = 0.012; HR为0.349; 95%CI为0.153-0.797）。虽然Nrf 2高表达的患者表现出更好的总生存率和无病生存率，该协会是没有统计学意义的Conclusions：高细胞质Keap 1表达，这可能会阻止核转位的Nrf 2在卵巢癌细胞，与较低的疾病复发率和死亡率。生存分析提示Keap 1表达可能在预测卵巢癌预后中起作用。
Objective: This study evaluated the expression patterns of nuclear factor erythroid 2-related factor 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) and assessed their clinical value as prognostic indicators in ovarian cancer.Methods: The expression patterns of Nrf2 and Keap1 were determined in 100 epithelial ovarian cancers by immunohistochemistry analyses. The associations of Nrf2 and Keap1 expression with clinicopathological characteristics of patients were evaluated. All patients received platinum-based chemotherapy. Chemoresistance was defined as recurrence within 6 months of first-line chemotherapy.Results: Cytoplasmic expression of Nrf2 and Keap1 was observed in 95% and 72%, respectively, of all 100 epithelial ovarian cancers examined. Low Keap1 expression (intensity= 1) was strongly predictive of better overall survival (P = 0.049) and disease-free survival (P = 0.004). Cox regression analysis indicated that Keap1 expression was an independent prognostic factor for overall survival (P = 0.012; HR, 0.349; 95% CI, 0.153-0.797). Although patients with high Nrf2 expression displayed better overall survival and disease-free survival, the association was not statistically significant.Conclusions: High cytoplasmic Keap1 expression, which might prevent nuclear translocation of Nrf2 in ovarian cancer cells, was associated with lower disease recurrence and death rate. Survival analysis suggested a probable role of Keap1 expression in predicting the prognosis of ovarian cancer.