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National Institute of Environmental Health Sciences

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Publication Detail

Title: Global Level of Plasma DNA Methylation is Associated with Overall Survival in Patients with Hepatocellular Carcinoma.

Authors: Yeh, Chih-Ching; Goyal, Abhishek; Shen, Jing; Wu, Hui-Chen; Strauss, Joshua A; Wang, Qiao; Gurvich, Irina; Safyan, Rachael A; Manji, Gulam A; Gamble, Mary V; Siegel, Abby B; Santella, Regina M

Published In Ann Surg Oncol, (2017 Nov)

Abstract: The impact of folate deficiency on global DNA methylation is uncertain. It also is unclear whether global DNA methylation is associated with outcome in HCC. LINE-1 methylation levels, as a surrogate marker of global methylation, may be influenced by folate deficiency. However, the interaction between LINE-1 methylation and folate level on overall survival (OS) in hepatocellular carcinoma (HCC) patients is unknown. We evaluated whether LINE-1 hypomethylation and folate deficiency are associated with HCC prognosis.We prospectively recruited 172 HCC patients between 2008 and 2012. LINE-1 methylation levels in plasma and white blood cells (WBC) were measured by pyrosequencing, and plasma folate levels by a radioprotein-binding assay.Patients with plasma LINE-1 methylation <70.0% (hypomethylation) had significantly worse OS compared with those with ≥70.0% methylation (hypermethylation) [hazard ratio (HR) = 1.77; 95% confidence interval (CI) 1.12-2.79; P = 0.015]. HCC patients with lower plasma folate levels also had worse survival (<27.7 vs. ≥27.7 nmol/L; HR = 1.96; 95% CI, 1.24-3.09; P = 0.004). Furthermore, survival was poor in patients in whom both plasma LINE-1 methylation and folate levels were low compared with those patients in whom both levels were high (HR = 3.36; 95%CI, 1.77-6.40; P < 0.001). This interaction neared statistical significance (P = 0.057). No significant association was found between WBC LINE-1 methylation levels and survival.These findings suggest that both lower plasma levels of LINE-1 methylation and folate are associated with worse survival in HCC patients.

PubMed ID: 28593503 Exiting the NIEHS site

MeSH Terms: No MeSH terms associated with this publication

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