Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma

Shoichi Inokuchi, Shinji Itoh, Tomoharu Yoshizumi, Kyohei Yugawa, Shohei Yoshiya, Takeo Toshima, Kazuki Takeishi, Tomohiro Iguchi, Kensaku Sanefuji, Noboru Harada, Keishi Sugimachi, Toru Ikegami, Kenichi Kohashi, Kenichi Taguchi, Hirotoshi Yonemasu, Kengo Fukuzawa, Yoshinao Oda, Masaki Mori

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Objectives: 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: 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: 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: Low mitochondrial OGG1 expression might aggravate the PDAC prognosis.

Original languageEnglish
Pages (from-to)1175-1182
Number of pages8
JournalPancreatology
Volume20
Issue number6
DOIs
Publication statusPublished - Sep 2020

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Hepatology
  • Gastroenterology

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