title: Whole-genome DNA methylation and hydroxymethylation profiling for HBV-related hepatocellular carcinoma.
abstract: Hepatocellular carcinoma (HCC) is a common solid tumor worldwide with a poor prognosis. Accumulating evidence has implicated important regulatory roles of epigenetic modifications in the occurrence and progression of HCC. In the present study, we analyzed 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) levels in the tumor tissues and paired adjacent peritumor tissues (APTs) from four individual HCC patients using a (hydroxy)methylated DNA immunoprecipitation approach combined with deep sequencing [(h)MeDIP-Seq]. Bioinformatics analysis revealed that the 5-mC levels in the promoter regions of 2796 genes and the 5-hmC levels in 507 genes differed significantly between HCC tissues and APTs. These differential genes were grouped into various clusters and pathways and found to be particularly enriched in the 'metabolic pathways' that include 'Glycolysis/gluconeogenesis', 'Oxidative phosphorylation' and 'Citrate cycle (TCA cycle)', implicating a potential role of metabolic alterations in HCC. Furthermore, 144 genes had both 5-mC and 5-hmC changes in HCC patients, and 10 of them (PCNA, MDM2, STAG1, E2F4, FGF4, FGF19, RHOBTB2, UBE2QL1, DCN and HSP90AA1) were enriched and interconnected in five pathways including the 'Cell cycle', 'Pathway in cancer', 'Ubiquitin mediated proteolysis', 'Melanoma' and 'Prostate cancer' pathways. The genome-wide mapping of 5-mC and 5-hmC in HCC tissues and APTs indicated that both 5-mC and 5-hmC epigenetic modifications play important roles in the regulation of HCC, and there may be some interconnections between them. Taken together, in the present study we conducted the first genome-wide mapping of DNA methylation combined with hydroxymethylation in HBV-related HCC and provided a series of potential novel epigenetic biomarkers for HCC.
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ye
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Tao
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Cao
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Danhua
authors.initials: D
authors.lastname: Zhu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Yini
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Ermei
authors.initials: E
authors.lastname: Chen
authors.affiliation: State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China.
authors.forename: Lanjuan
authors.initials: L
authors.lastname: Li
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D019175:DNA Methylation; D055106:Genome-Wide Association Study; D006515:Hepatitis B virus / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000821:virology*; D011401:Promoter Regions, Genetic
chemical_list: C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine