Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma
Mitochondrial expression of the DNA repair enzyme OGG1 improves the prognosis of pancreatic ductal adenocarcinoma
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DOI：
10.1016/j.pan.2020.07.011
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发表时间：
2020-09-01
期刊：
影响因子：
3.6
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Inokuchi, Shoichi;Itoh, Shinji;Mori, Masaki
背景/目的：8-羟基脱氧鸟苷（8-OHdG）是氧化应激的指示剂，可引起颠换突变和致癌作用。8-OHdG由8-OHdG DNA糖基化酶1（OGG 1）切除修复，OGG 1被分类为核和线粒体亚型。我们的目的是阐明OGG 1在胰腺导管腺癌（PDAC）中的作用。方法：对92例在多个机构接受手术切除的PDAC患者进行免疫组化分析。使用Germann免疫反应性评分对OGG 1和8-OHdG表达水平进行评分。结果：核OGG 1低表达组（n = 41）的糖链抗原（CA）19-9（p = 0.026）和s-胰腺抗原（SPAN）-1（p = 0.017）显著高于核OGG 1高表达组（n = 51）。核OGG 1表达对预后无影响。与高表达组（n = 52）相比，线粒体OGG 1低表达组（n = 40）显示出更高的CA 19 -9（p = 0.041）、更高的SPAN-1（p = 0.032）和更多的组织学神经周围浸润（p = 0.037）。低线粒体OGG 1表达组的无复发生存率（p = 0.0080）和总生存率（p = 0.0073）显著较短。考克斯比例风险模型显示线粒体OGG 1低表达是PDAC预后的独立危险因素。OGG 1表达与8-OHdG表达呈负相关（p = 0.0004），8-OHdG高表达可缩短PDAC患者的无复发生存期。(C)2020年IAP和EPC。Elsevier B. V.出版，保留所有权利。
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. (C) 2020 IAP and EPC. Published by Elsevier B.V. All rights reserved.