Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma.
8-Hydroxy-2'-Deoxyguanosine
Adult
CA-19-9 Antigen
Carcinoma, Pancreatic Ductal
/ metabolism
Cell Nucleus
/ metabolism
DNA Glycosylases
/ biosynthesis
Female
Humans
Male
Middle Aged
Mitochondria
/ metabolism
Pancreatic Neoplasms
/ metabolism
Prognosis
Retrospective Studies
Risk Factors
Survival Analysis
8-OHdG
Cancer
Pancreas
Prognosis
ROS
Journal
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
ISSN: 1424-3911
Titre abrégé: Pancreatology
Pays: Switzerland
ID NLM: 100966936
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
29
02
2020
revised:
05
07
2020
accepted:
17
07
2020
pubmed:
4
8
2020
medline:
27
8
2021
entrez:
4
8
2020
Statut:
ppublish
Résumé
8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC). Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined. The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC. Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.
Sections du résumé
BACKGROUND/OBJECTIVES
OBJECTIVE
8-Hydroxydeoxyguanosine (8-OHdG) is an indicator of oxidative stress and causes transversion mutations and carcinogenesis. 8-OHdG is excision repaired by 8-OHdG DNA glycosylase 1 (OGG1), which is classified as nuclear and mitochondrial subtypes. We aimed to clarify the role of OGG1 in pancreatic ductal adenocarcinoma (PDAC).
METHODS
METHODS
Ninety-two patients with PDAC who had undergone surgical resection at multiple institutions were immunohistochemically analyzed. The OGG1 and 8-OHdG expression levels were scored using the Germann Immunoreactive Score. The cutoff values of OGG1, as well as that of 8-OHdG, were determined.
RESULTS
RESULTS
The low nuclear OGG1 expression group (n = 41) showed significantly higher carbohydrate antigen (CA)19-9 (p = 0.026), and higher s-pancreas antigen (SPAN)-1 (p = 0.017) than the high expression group (n = 51). Nuclear OGG1 expression has no effect on the prognosis. The low mitochondrial OGG1 expression group (n = 40) showed higher CA19-9 (p = 0.041), higher SPAN-1 (p = 0.032), and more histological perineural invasion (p = 0.037) than the high expression group (n = 52). The low mitochondrial OGG1 expression group had a significantly shorter recurrence-free survival (p = 0.0080) and overall survival (p = 0.0073) rates. The Cox proportional hazards model revealed that low mitochondrial OGG1 expression is an independent risk factor of the PDAC prognosis. OGG1 expression was negatively correlated with 8-OHdG expression (p = 0.0004), and high 8-OHdG expression shortened the recurrence-free survival of patients with PDAC.
CONCLUSIONS
CONCLUSIONS
Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.
Identifiants
pubmed: 32741713
pii: S1424-3903(20)30226-X
doi: 10.1016/j.pan.2020.07.011
pii:
doi:
Substances chimiques
CA-19-9 Antigen
0
8-Hydroxy-2'-Deoxyguanosine
88847-89-6
DNA Glycosylases
EC 3.2.2.-
oxoguanine glycosylase 1, human
EC 3.2.2.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1175-1182Informations de copyright
Copyright © 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare no conflicts of interest.