Keap1 expression has independent prognostic value in pancreatic adenocarcinomas

Diagnostic Pathology

Peeter Karihtala³  Ylermi Soini¹  Kirsi-Maria Haapasaari²  Joel Isohookana³ 

[1] Department of Pathology and Forensic Medicine, University of Eastern Finland, Cancer Center of Eastern Finland, Kuopio, 70211, Finland;Department of Pathology, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu University Hospital, 90020, Finland;Department of Oncology and Radiotherapy, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu University Hospital, 90029, Finland

关键词: Pancreatic cancer;    Oxidative stress;    Nrf2;    Keap1;    Antioxidant enzymes;    8-hydroxydeoxyguanosine;   

Others  :  1217781
DOI  :  10.1186/s13000-015-0258-4

 received in 2014-08-27, accepted in 2015-03-25,  发布年份 2015

【 摘 要 】

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.

Virtual slides

The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/4220521801406476 webcite

【 授权许可】

   
2015 Isohookana et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

Figure 2.

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