Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Pathol Int. 2020 Aug;70(8):533-541. doi: 10.1111/pin.12952. Epub 2020 May 17.
Hepatocellular carcinoma (HCC) has a poor prognosis in the setting of chronic inflammation and fibrosis, both of which promote nuclear DNA oxidative damage. 8-hydroxy-deoxyguanosine (8-OHdG) DNA glycosylase (OGG1) enhances the repair of 8-OHdG, which is the primary oxidative stress-induced mutation that leads to malignant alterations. This study aims to clarify the relationships between oxidative stress-induced factors and HCC progression. The clinicopathological factors were compared with immunohistochemistry OGG1 and 8-OHdG expressions in 86 resected HCC specimens. High 8-OHdG expression was associated with high serum aspartate transaminase and total bilirubin levels, as well as a low platelet count, compared with low 8-OHdG expression. Histological liver cirrhosis and poor differentiation were more frequent in patients with high 8-OHdG expression than in those with low 8-OHdG expression. The 8-OHdG was negatively correlated with OGG1 expression in HCC patients. Therefore, we classified the patients into two groups, low OGG1/high 8-OHdG group and the other group. The patients with low OGG1/high 8-OHdG expressions had worse prognosis than those with the other expressions. Our results showed that low OGG1/high 8-OHdG expressions in nuclei influence HCC patient outcomes. Evaluating the patterns of OGG1 and 8-OHdG expressions might provide pivotal prognostic biomarkers in patients with HCC.
肝细胞癌 (HCC) 在慢性炎症和纤维化的情况下预后不良，这两者都促进核 DNA 氧化损伤。8-羟基脱氧鸟苷 (8-OHdG) DNA 糖苷酶 (OGG1) 增强了 8-OHdG 的修复，8-OHdG 是导致恶性改变的主要氧化应激诱导突变。本研究旨在阐明氧化应激诱导因素与 HCC 进展之间的关系。在 86 例切除的 HCC 标本中，将临床病理因素与免疫组织化学 OGG1 和 8-OHdG 表达进行了比较。与低 8-OHdG 表达相比，高 8-OHdG 表达与高血清天冬氨酸转氨酶和总胆红素水平以及低血小板计数相关。与低 8-OHdG 表达相比，高 8-OHdG 表达的患者更常出现组织学肝硬化和低分化。在 HCC 患者中，8-OHdG 与 OGG1 表达呈负相关。因此，我们将患者分为两组，低 OGG1/高 8-OHdG 组和另一组。低 OGG1/高 8-OHdG 表达的患者预后比其他表达的患者差。我们的结果表明，核内低 OGG1/高 8-OHdG 表达影响 HCC 患者的预后。评估 OGG1 和 8-OHdG 表达模式可能为 HCC 患者提供关键的预后生物标志物。
