NRF2, DJ1 and SNRX1 and their prognostic impact in astrocytic gliomas
NRF2, DJ1 and SNRX1 and their prognostic impact in astrocytic gliomas
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DOI：
10.14670/hh-11-973
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发表时间：
2018-08-01
影响因子：
2
通讯作者：
Soini, Ylermi
中科院分区：
文献类型：
--
作者：
Haapasalo, Joonas;Nordfors, Kristiina;Soini, Ylermi
核因子红细胞2相关因子2（NRF 2）、DJ 1和硫氧还蛋白1（SRXN 1）是保护细胞免受活性氧引起的氧化损伤的转录因子，另一方面，与癌症治疗的抗性相关。NRF 2、DJ 1和SRNX 1的免疫组化表达在人类II-IV级星形胶质细胞瘤中进行了评估。评估了它们与临床病理和基本分子因素的关系。从公开可用的数据集分析RNA表达水平和遗传改变。所有研究的分子都是共同表达的。细胞质NRF 2表达在恶性程度较高的肿瘤中较高，而细胞核和细胞质DJ 1表达与恶性程度较低相关。异柠檬酸脱氢酶1突变（IDH 1）的存在与NRF 2的细胞质和细胞核表达以及细胞核DJ 1表达的增加相关。当将原发性IV级星形细胞瘤与继发性胶质母细胞瘤进行比较时，核DJ 1与继发性肿瘤相关。在II-IV级肿瘤中，细胞质NRF 2表达与预后不良相关，而细胞核NRF 2以及细胞质和细胞核DJ 1与患者预后较好相关。观察到DJ 1的复发性纯合缺失，特别是在IDH野生型样品中。当只评估胶质母细胞瘤时，核NRF 2和SRNX 1预测更好的生存率。因此，NRF 2、DJ 1和SNXR 1可作为胶质瘤的肿瘤标志物。
Nuclear factor erythroid 2-related factor 2 (NRF2), DJ1 and sulfiredoxin 1 (SRXN1) are transcription factors which protect cells from the oxidative damage caused by reactive oxygen species and, on the other hand, are associated with resistance to cancer treatments. The immunohistochemical expression of NRF2, DJ1 and SRNX 1 was assessed in human grade II-IV astrocytic gliomas. Their association to clinicopathologic and essential molecular factors was evaluated. The RNA expression levels and genetic alterations were analyzed from publicly available datasets. All studied molecules were commonly expressed. The cytoplasmic NRF2 expression was higher in tumors with a higher malignancy grade, whereas the nuclear and cytoplasmic DJ1 expression was associated with a lower grade. The presence of the isocitrate dehyrdogenase 1 mutation (IDH1) was associated with an increasing cytoplasmic and nuclear expression of NRF2 and a nuclear DJ1 expression. When primary grade IV astrocytomas were compared to secondary glioblastomas, nuclear DJ1 was associated with secondary tumors. In grade II-IV tumors, the cytoplasmic NRF2 expression was associated with a poor prognosis, whereas nuclear NRF2 and both cytoplasmic and nuclear DJ1 were associated with a better patient prognosis. Recurrent homozygous deletions of DJ1 were observed, especially in the IDH wild-type samples. When only the glioblastomas were evaluated, nuclear NRF2 and SRNX1 predicted better survival. As a conclusion, NRF2, DJ1 and SNXR1 can be used as prognosticators in gliomas.