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

研究成果: ジャーナルへの寄稿学術誌査読

1 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)1175-1182
ページ数8
ジャーナルPancreatology
20
6
DOI
出版ステータス出版済み - 9月 2020

!!!All Science Journal Classification (ASJC) codes

  • 内分泌学、糖尿病および代謝内科学
  • 肝臓学
  • 消化器病学

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