ISSN: 1837-9664Journal of Cancer
Global reach, higher impact
J Cancer 2021; 12(13):4064-4074. doi:10.7150/jca.56982 This issue Cite
Research Paper
The lipid peroxidation derived DNA adduct γ-OHPdG levels in paraneoplastic liver tissues predict postoperative outcomes of hepatoma
1. Department of Gastroenterology & Hepatology, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
2. Department of internal medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
3. College of Medicine, Chang Gung University, Taoyuan, Taiwan.
4. Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan.
Abstract
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 (P = 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 (P = 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 (P = 0.016) and distant metastasis-free survival (P = 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). In vitro 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.
Keywords: hepatocellular carcinoma, lipid peroxidation, γ-OHPdG, survival outcome, biomarker
Citation styles
