University of Oulu

Immonen, A., Haapasaari, K.-M., Skarp, S., Karihtala, P., & Teppo, H.-R. (2022). Nrf3 decreases during melanoma carcinogenesis and is an independent prognostic marker in melanoma. Oxidative Medicine and Cellular Longevity, 2022, 1–10.

NRF3 decreases during melanoma carcinogenesis and Is an independent prognostic marker in melanoma

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Author: Immonen, Anni1,2; Haapasaari, Kirsi-Maria1,2,3; Skarp, Sini4;
Organizations: 1Cancer Research and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
2Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
3Department of Pathology, Oulu University Hospital, Oulu, Finland
4Infrastructure for Population Studies, Faculty of Medicine, University of Oulu, Oulu, Finland
5Helsinki University Hospital Comprehensive Cancer Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 2.2 MB)
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Language: English
Published: Hindawi, 2022
Publish Date: 2022-09-30


The prognostic significance of the major redox regulator, nuclear factor erythroid-2-related factor 2 (NRF2), is recognized in many cancers, but the role of NRF3 is not studied. Analysis from the Gene Expression Omnibus datasets showed that NRF3 mRNA levels increased from benign to dysplastic naevi (p = 0.04). We characterized the immunohistochemical expression of NRF3 in 81 naevi, 67 primary skin melanomas, and 51 lymph node metastases. The immunohistochemical expression of cytoplasmic NRF3 decreased from benign to dysplastic naevi (p < 0.001) and further to primary melanomas (p < 0.001). High cytoplasmic NRF3 protein expression in pigment cells of the primary melanomas associated with worse melanoma-specific survival in multivariate analysis, specifically in the subgroup of patients with the lymph node metastases at the time of diagnosis (hazard ratio 3.179; 95% confidence interval 1.065-9.493; p = 0.038). Intriguingly, we did not observe associations between NRF3 and the traditional prognostic factors such as Breslow thickness, ulceration, or stage. Together, this data represents the primary description about the role of NRF3 in pigment tumours that is worthy of further explorations.

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Series: Oxidative medicine and cellular longevity
ISSN: 1942-0900
ISSN-E: 1942-0994
ISSN-L: 1942-0900
Volume: 2022
Article number: 2240223
DOI: 10.1155/2022/2240223
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Funding: We thank the Finnish Dermatopathology Association and Finnish Society for Oncology, Melanoma group, for the financial support in the form of personal grants (HRT) and Medical Research Center Oulu in the form of working grants (HRT).
Copyright information: © 2022 Anni Immonen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.