title: Association of 5-methylcytosine and 5-hydroxymethylcytosine with mitochondrial DNA content and clinical and biochemical parameters in hepatocellular carcinoma.
abstract: Increasing epidemiological evidence has indicated that inherited variations of mitochondrial DNA (mtDNA) copy number affect the genetic susceptibility of many malignancies in a tumour-specific manner and that DNA methylation also plays an important role in controlling gene expression during the differentiation and development of hepatocellular carcinoma (HCC). Our previous study demonstrated that HCC tissues showed a lower 5-hydroxymethylcytosine (5-hmC) content when compared to tumour-adjacent tissues, but the relationship among 5-hmC, 5-methylcytosine (5-mC) and mtDNA content in HCC patients is still unknown. This study aimed to clarify the correlation among mtDNA content, 5-mC and 5-hmC by quantitative real-time PCR and liquid chromatography tandem mass spectrometry analysis. We demonstrated that 5-hmC correlated with tumour size [odds ratio (OR) 0.847, 95% confidence interval (CI) 0.746-0.962, P = 0.011], and HCC patients with a tumour size ≥ 5.0 cm showed a lower 5-hmC content and higher levels of fasting plasma aspartate aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, γ-glutamyltransferase, alpha-fetoprotein than those with a tumour size <5 cm (all P<0.05). We further revealed that the mtDNA content of HCC tumour tissues was 225.97(105.42, 430.54) [median (25th Percentile, 75th Percentile)] and was negatively correlated with 5-mC content (P = 0.035), but not 5-hmC content, in genomic DNA from HCC tumour tissues.
authors.affiliation: Center for Gene Diagnosis, Medical Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Shen
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Jia-Hui
authors.initials: JH
authors.lastname: Qi
authors.forename: Bi-Feng
authors.initials: BF
authors.lastname: Yuan
authors.forename: Jing-Tao
authors.initials: JT
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.forename: Yu-Qi
authors.initials: YQ
authors.lastname: Feng
authors.forename: Ying-Juan
authors.initials: YJ
authors.lastname: Liu
authors.forename: Song-Mei
authors.initials: SM
authors.lastname: Liu
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism* / Q000031:analogs & derivatives; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D004272:DNA, Mitochondrial; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine