Prediagnostic levels of urinary 8-epi-prostaglandin F and prostaglandin E2 metabolite, biomarkers of oxidative damage and inflammation, and risk of hepatocellular carcinoma

Jian Min Yuan, Menno Grouls, Steven G. Carmella, Renwei Wang, Alisa Heskin, Yang Jiang, Yu Ting Tan, Jennifer Adams-Haduch, Yu Tang Gao, Stephen S. Hecht

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Chronic inflammation and oxidative stress play pivotal roles in the pathogenesis of hepatocellular carcinoma (HCC). We conducted a nested case-control study of 347 HCC cases and 691 matched controls within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F (8-epi-PGF), a biomarker of oxidative stress, and prostaglandin E2 (PGE2) metabolite (PGE-M), a biomarker of the inflammation mediator PGE2, were determined in baseline urine samples using validated mass spectrometry assays. 8-epi-PGF levels were significantly higher in HCC cases than control subjects (geometric means 0.92 versus 0.80 pmol/mg creatinine, P < 0.001). The relative risks of developing HCC for the highest relative to the lowest quartile of 8-epi-PGF were 2.55 (95% confidence interval = 1.62-4.01, Ptrend < 0.001). This positive 8-epi-PGF-HCC risk association was independent of smoking status, alcohol consumption and hepatitis B or liver cirrhosis and was present 10 years before the clinical manifestation of HCC. This study did not find any significant association between urinary PEG-M and HCC risk. This study provides direct evidence in support of the critical role of oxidative stress in the development of HCC regardless of its underlying causes.

Original languageEnglish (US)
Pages (from-to)989-997
Number of pages9
Issue number8
StatePublished - Aug 22 2019

Bibliographical note

Funding Information:
USPHS grant (R01CA 043092, R01 CA129534, R01 CA144034, R01 CA81301 and UM1 CA182876). Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, supported in part by Cancer Center Support grant (CA-77598).

Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email:

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