Feng Yang-Yi, Yu Jen, Huang Yi Hsuan, Lin Yang-Hsiang, Yeh Chau-Ting
Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Department of internal medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
J Cancer. 2021 May 13;12(13):4064-4074. doi: 10.7150/jca.56982. eCollection 2021.
Chronic necroinflammation in liver induces lipid peroxidation and oxidative stress, which contributes to hepatocellular carcinoma (HCC) development. Gamma-hydroxy-1, N2-propanodeoxyguanosine (γ-OHPdG), a promutagenic DNA adduct, is derived from lipid peroxidation. Little is known about the clinical roles of γ-OHPdG in relationship to HCC progression. Here, we showed that γ-OHPdG levels were highly expressed in the cancerous HCC tissues ( = 0.020, compared to those in noncancerous parts). Postoperative outcome analysis revealed that higher γ-OHPdG expression in the paraneoplastic noncancerous tissues was independently associated with shorter distant metastasis-free survival ( = 0.020). In subgroup analysis, higher γ-OHPdG expression in the noncancerous tissues in hepatitis B related HCC subgroup was associated with shorter overall survival ( = 0.016) and distant metastasis-free survival ( = 0.006). However, in patient subgroups including non-cirrhosis, bilirubin < 1.2 mg/dL, alanine transaminase < 41 U/L, or aspartate transaminase < 31 U/L, higher γ-OHPdG expression in the cancerous tissues was associated with longer overall survival (P < 0.03 for all). experiments showed that cell viability was suppressed upon hydrogen peroxide treatment in liver cancer cell lines. In conclusion, lipid peroxidation derived marker, γ-OHPdG, in the paraneoplastic noncancerous and cancerous liver tissues predicted postoperative outcomes in HCC patients.
肝脏中的慢性坏死性炎症会诱导脂质过氧化和氧化应激,这有助于肝细胞癌(HCC)的发展。γ-羟基-1,N2-丙基脱氧鸟苷(γ-OHPdG)是一种促突变DNA加合物,源自脂质过氧化。关于γ-OHPdG在HCC进展中的临床作用知之甚少。在此,我们发现γ-OHPdG水平在癌性HCC组织中高表达(与非癌部分相比,P = 0.020)。术后结果分析显示,癌旁非癌组织中较高的γ-OHPdG表达与较短的无远处转移生存期独立相关(P = 0.020)。在亚组分析中,乙型肝炎相关HCC亚组的非癌组织中较高的γ-OHPdG表达与较短的总生存期(P = 0.016)和无远处转移生存期(P = 0.006)相关。然而,在包括无肝硬化、胆红素<1.2mg/dL、丙氨酸转氨酶<41U/L或天冬氨酸转氨酶<31U/L的患者亚组中,癌组织中较高的γ-OHPdG表达与较长的总生存期相关(所有P均<0.03)。实验表明,在肝癌细胞系中,过氧化氢处理后细胞活力受到抑制。总之,癌旁非癌和癌性肝组织中脂质过氧化衍生标志物γ-OHPdG可预测HCC患者的术后结果。