Haapasalo Joonas, Nordfors Kristiina, Granberg Kirsi J, Kivioja Tomi, Nykter Matti, Haapasalo Hannu, Soini Ylermi
Unit of Neurosurgery, Tampere University Hospital, Tampere, Finland.
Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
Histol Histopathol. 2018 Aug;33(8):791-801. doi: 10.14670/HH-11-973. Epub 2018 Feb 14.
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 SRNX1 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.
核因子红细胞2相关因子2（NRF2）、DJ1和硫氧还蛋白1（SRXN1）是转录因子，它们可保护细胞免受活性氧引起的氧化损伤，另一方面，它们与癌症治疗耐药性相关。在人类II-IV级星形胶质细胞瘤中评估了NRF2、DJ1和SRNX1的免疫组化表达。评估了它们与临床病理和重要分子因素的关联。从公开可用的数据集中分析了RNA表达水平和基因改变。所有研究的分子均普遍表达。恶性程度较高的肿瘤中细胞质NRF2表达较高，而细胞核和细胞质DJ1表达与较低级别相关。异柠檬酸脱氢酶1突变（IDH1）的存在与NRF2的细胞质和细胞核表达增加以及DJ1的细胞核表达相关。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，细胞核DJ1与继发性肿瘤相关。在II-IV级肿瘤中，细胞质NRF2表达与预后不良相关，而细胞核NRF2以及细胞质和细胞核DJ1均与患者预后较好相关。观察到DJ1存在反复的纯合缺失，尤其是在IDH野生型样本中。仅评估胶质母细胞瘤时，细胞核NRF2和SRNX1预示着更好的生存率。总之，NRF2、DJ1和SNXR1可作为胶质瘤的预后指标。
