Keap1 expression has independent prognostic value in pancreatic adenocarcinomas
| Autor: | Joel Isohookana, Ylermi Soini, Peeter Karihtala, Kirsi-Maria Haapasaari |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Pathology
medicine.medical_specialty Keap1 Histology Time Factors Cellular differentiation Regulator Kaplan-Meier Estimate Biology Adenocarcinoma medicine.disease_cause Disease-Free Survival Nrf2 Pathology and Forensic Medicine Risk Factors Pancreatic cancer Cause of Death medicine Biomarkers Tumor Humans 8-hydroxydeoxyguanosine Proportional Hazards Models Chi-Square Distribution Kelch-Like ECH-Associated Protein 1 Research Intracellular Signaling Peptides and Proteins 8-Hydroxy-2'-deoxyguanosine Deoxyguanosine Cell Differentiation General Medicine medicine.disease KEAP1 Immunohistochemistry Tumor Burden Pancreatic Neoplasms Oxidative Stress Treatment Outcome Oxidative stress 8-Hydroxy-2'-Deoxyguanosine Lymphatic Metastasis Multivariate Analysis Antioxidant enzymes Oxidation-Reduction |
| Zdroj: | Diagnostic Pathology |
| ISSN: | 1746-1596 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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