University of Oulu

Isohookana, J., Haapasaari, KM., Soini, Y. et al. Keap1 expression has independent prognostic value in pancreatic adenocarcinomas. Diagn Pathol 10, 28 (2015). https://doi.org/10.1186/s13000-015-0258-4

Keap1 expression has independent prognostic value in pancreatic adenocarcinomas

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Author: Isohookana, Joel1,2,3; Haapasaari, Kirsi-Maria1; Soini, Ylermi2;
Organizations: 1Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 50, 90020, Oulu University Hospital, Finland
2Department of Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland
3Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, P.O. Box 22, 90029, Oulu University Hospital, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2021112657184
Language: English
Published: Springer Nature, 2015
Publish Date: 2021-11-26
Description:

Abstract

Background: Oxidative stress and redox-regulating enzymes may potentially accelerate pancreatic carcinogenesis and also affect chemoresistance. Recently major antioxidant response regulator NF-E2-related factor 2 (Nrf2) has been linked to poor prognosis in pancreatic cancer. Nrf2 activity is strictly regulated by oxidative stress sensor Kelch-like ECH-associated protein 1 (Keap1). Oxidative DNA damage can be estimated e.g. by 8-hydroxy-2′-deoxyguanosine (8-OHdG) expression. The aim of this study was to evaluate the expression and possible prognostic role of Keap1 and 8-OHdG in pancreatic cancer.

Methods: We assessed immunohistochemically the expression of 8-OHdG and Keap1 in precisely characterized material of 69 pancreatic adenocarcinoma patients.

Results: Nuclear 8-OHdG associated with cytoplasmic Keap1 expression (p = 0.031) and was overexpressed in patients with smaller tumors (p = 0.016) and in tumors without lymph node involvement (p = 0.051). Cytoplasmic 8-OHdG expression associated with higher differentiation (p = 0.023). Cytoplasmic Keap1 immunostaining associated with N0-staging (p = 0.0009) and the absence of distant metastases (p = 0.018). Membranous Keap1 associated with longer relapse-free survival (p = 0.041) and pancreatic cancer-specific survival (median survival 14 vs. 32 months; p = 0.029) and was in multivariate analysis an independent prognostic factor of pancreatic cancer-related death (HR 2.66, 95%CI 1.23–5.75).

Conclusions: Oxidative stress and main redox regulators may participate in pancreatic carcinogenesis and Keap1 appears as a promising prognostic factor in pancreatic cancer. Future studies should also concentrate on potential link between redox regulation and chemoresistance in pancreatic cancer.

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Series: Diagnostic pathology
ISSN: 1746-1596
ISSN-E: 1746-1596
ISSN-L: 1746-1596
Volume: 10
Article number: 28
DOI: 10.1186/s13000-015-0258-4
OADOI: https://oadoi.org/10.1186/s13000-015-0258-4
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
Subjects:
Copyright information: © 2015 Isohookana et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
  https://creativecommons.org/licenses/by/4.0/