{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T17:40:22Z","timestamp":1771350022626,"version":"3.50.1"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T00:00:00Z","timestamp":1510531200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2017,11,13]],"date-time":"2017-11-13T00:00:00Z","timestamp":1510531200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>Hepatocellular carcinoma (HCC) is the third leading cause of cancer\u2013related deaths worldwide, mainly because of its poor prognosis. A valid mechanism\u2010based prognostic biomarker is urgently needed. \u03b3\u2010hydroxy\u20101,<jats:italic toggle=\"yes\">N<\/jats:italic>\n                           <jats:sup>2<\/jats:sup>\u2010propanodeoxyguanosine (\u03b3\u2010OHPdG) is an endogenously formed mutagenic DNA adduct derived from lipid peroxidation. We examined the relationship of \u03b3\u2010OHPdG with hepatocarcinogenesis in two animal models and its potential role as a prognostic biomarker for recurrence in HCC patients. Bioassays were conducted in xeroderma pigmentosum group A knockout mice and diethylnitrosamine\u2010injected mice, both prone to HCC development. \u03b3\u2010OHPdG levels in the livers of these animals were determined. The effects of antioxidant treatments on \u03b3\u2010OHPdG and hepatocarcinogenesis were examined. Using two independent sets of HCC specimens from patients, we examined the relationship between \u03b3\u2010OHPdG and survival or recurrence\u2010free survival. \u03b3\u2010OHPdG levels in liver DNA showed an age\u2010dependent increase and consistently correlated with HCC development in all three animal models. Theaphenon E treatment significantly decreased \u03b3\u2010OHPdG levels in the liver DNA of xeroderma pigmentosum group A knockout mice and remarkably reduced HCC incidence in these mice to 14% from 100% in the controls. It also effectively inhibited HCC development in the diethylnitrosamine\u2010injected mice. Using clinical samples from two groups of patients, our study revealed that higher levels of \u03b3\u2010OHPdG are strongly associated with low survival (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; 0.0001) and low recurrence\u2010free survival (<jats:italic toggle=\"yes\">P<\/jats:italic> = 0.007). <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic> These results support \u03b3\u2010OHPdG as a mechanism\u2010based, biologically relevant biomarker for predicting the risk of HCC and its recurrence. (H<jats:sc>epatology<\/jats:sc> 2018;67:159\u2010170).<\/jats:p>","DOI":"10.1002\/hep.29380","type":"journal-article","created":{"date-parts":[[2017,7,18]],"date-time":"2017-07-18T12:49:15Z","timestamp":1500382155000},"page":"159-170","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["An endogenous DNA adduct as a prognostic biomarker for hepatocarcinogenesis and its prevention by Theaphenon E in mice"],"prefix":"10.1097","volume":"67","author":[{"given":"Ying","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center,Georgetown University,Washington,DC"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shana","family":"Silverstein","sequence":"additional","affiliation":[{"name":"Department of Oncology, Lombardi Comprehensive Cancer Center,Georgetown 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