Nuclear factor erythroid 2-related factors 1 and 2 are able to define the worst prognosis group among high-risk diffuse large B cell lymphomas treated with R-CHOEP
Nuclear factor erythroid 2-related factors 1 and 2 are able to define the worst prognosis group among high-risk diffuse large B cell lymphomas treated with R-CHOEP
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DOI：
10.1136/jclinpath-2018-205584
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Kuittinen, Outi
中科院分区：
文献类型：
--
作者：
Kari, Esa;Teppo, Hanna-Riikka;Kuittinen, Outi
氧化应激标志物和抗氧化酶先前已被证明具有预后价值，并与弥漫性大 B 细胞淋巴瘤 (DLBCL) 患者的不良结局相关。核因子红细胞 2 相关因子 1 (Nrf1) 和因子 2 (Nrf2) 是抗氧化酶产生的主要诱导剂。 Kelch ECH 关联蛋白 1 (Keap1) 是 Nrf2 的负调节因子，BTB（BR-C、ttk 和 bab）结构域和 CNC 同源物 1 (Bach1) 抑制这两个因子的功能。它们在 DLBCL 预后中的意义尚不清楚。方法对 76 例高危 DLBCL 患者的诊断活检样本进行回顾性免疫组织化学染色，检测 Nrf1、Nrf2、Keap1 和 Bach1，并与临床数据和转归相关。结果Nrf2 和 Nrf2 与良好的临床表现相关（血红蛋白水平正常、无 B 症状、有限期）。所评估的因素均不能单独预测生存率。然而，当组合以下两个参数时：Nrf2 的高核评分、Nrf1 的低核评分、Nrf1 的高细胞质评分和 Keap1 的低细胞质评分与显着较差的总生存期相关。结论 Nrf1 和 Nrf2 与高危 DLBCL 的疾病表现和总生存期相关。 Nrf1 的低核表达、Nrf1 的高细胞质表达、Nrf2 的高核表达和 Keap1 的低细胞质表达与该患者组的不良结果相关。
Aims Oxidative stress markers and antioxidant enzymes have previously been shown to have prognostic value and associate with adverse outcome in patients with diffuse large B cell lymphoma (DLBCL). Nuclear factor erythroid 2-related factor 1 (Nrf1) and factor 2 (Nrf2) are among the principal inducers of antioxidant enzyme production. Kelch ECH associating protein 1 (Keap1) is a negative regulator of Nrf2, and BTB (BR-C, ttk and bab) domain and CNC homolog 1 (Bach1) represses the function of both factors. Their significance in DLBCL prognosis is unknown.Methods Diagnostic biopsy samples of 76 patients with high-risk DLBCL were retrospectively stained with immunohistochemistry for Nrf1, Nrf2, Keap1 and Bach1, and correlated with clinical data and outcome.Results Nuclear Nrf2 and nuclear Bach1 expression were associated with adverse clinical features (anaemia, advanced stage, high IPI, high risk of neutropaenic infections), whereas cytoplasmic Nrf1 and Nrf2 were associated with favourable clinical presentation (normal haemoglobin level, no B symptoms, limited stage). None of the evaluated factors could predict survival alone. However, when two of the following parameters were combined: high nuclear score of Nrf2, low nuclear score of Nrf1, high cytoplasmic score of Nrf1 and low cytoplasmic score of Keap1 were associated with significantly worse overall survival.Conclusions Nrf1 and Nrf2 are relevant in disease presentation and overall survival in high-risk DLBCL. Low nuclear expression of Nrf1, high cytoplasmic expression of Nrf1, high nuclear expression of Nrf2 and low cytoplasmic expression of Keap1 are associated with adverse outcome in this patient group.