From Cell Biology to Tissue Engineering


NRF2, DJ1 and SNRX1 and their prognostic impact in astrocytic gliomas

Joonas Haapasalo1, Kristiina Nordfors3,4, Kirsi J. Granberg2,5, Tomi Kivioja1,2, Matti Nykter2,5, Hannu Haapasalo6 and Ylermi Soini7

1Unit of Neurosurgery, 2Science Center, Tampere University Hospital, 3Department of Pediatrics, 4Tampere Center for Child Health Research, Tampere University Hospital, 5BioMediTech and Faculty of Medicine and Life Sciences, University of Tampere, 6Department of Pathology, Fimlab Laboratories, Tampere and 7Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland and Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland

Offprint requests to: Joonas Haapasalo, Unit of Neurosurgery, Tampere University Hospital, Teiskontie 35, FI-33521 Tampere, Finland. e-mail: joonas.haapasalo@gmail.com

Summary. 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. Histol Histopathol 33, 791-801 (2018)

Key words: NRF2, DJ1, SNXR1, Glioma, Prognosis

DOI: 10.14670/HH-11-973