title: Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients.
abstract: Hepatocellular carcinoma (HCC) is the fifth most common cancer and the fourth leading cause of cancer mortality globally. HCC incidence has doubled in Egypt in the past 10 years, which could be attributed to the high prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV), although HBV rates have declined after the introduction of the vaccine in 1992. Aberrant DNA methylation may play an important role in hepatocarcinogenesis. Liver biopsy is the current gold standard for methylation studies; however, imaging techniques often suffice for diagnosis making tissue samples increasingly scarce. The efficacy of conducting DNA methylation studies in molecular epidemiology using plasma DNA is still unclear. We compared tumor methylation profile for the tumor suppressor genes APC, FHIT, p15, p16, and E-cadherin in tumor tissues and plasma to test the concordance between the two types of specimen from the same HCC patients. Twenty-eight HCC patients with matching tissue and plasma DNA were recruited from a case-control study in Gharbiah, Egypt. Concordance between the tissue and plasma was statistically significant in all five genes as follows: APC (23/28, 82.1%, p=0.001), FHIT (24/28, 85.7%, p=.0001), p15 (25/28, 89.2%, p=0.045), p16 (19/28, 67.9%, p=0.037), and E-cadherin (22/28, 78.5%, p=0.0008). The average specificity was 90%, 86%, 96%, 86%, and 100%, respectively. There was no significant association between methylation and hepatitis viral infection for any of the genes tested in this study. Plasma DNA can be reliable for testing methylation profile in liver cancer patients in this population. Future studies on a larger sample size should investigate methylation profile in populations with higher rates of HBV, HCV, and other risk factors.
authors.affiliation: Department of Epidemiology, University of Michigan, School of Public Health, 109 Observatory Street, Ann Arbor, MI 48109, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Iyer
authors.forename: Abdel-Rahman
authors.initials: AR
authors.lastname: Zekri
authors.forename: Chu-Wei
authors.initials: CW
authors.lastname: Hung
authors.forename: Emily
authors.initials: E
authors.lastname: Schiefelbein
authors.forename: Kadry
authors.initials: K
authors.lastname: Ismail
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hablas
authors.forename: Ibrahim A
authors.initials: IA
authors.lastname: Seifeldin
authors.forename: Amr S
authors.initials: AS
authors.lastname: Soliman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000097:blood* / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood*; D004534:Egypt; D005260:Female; D020868:Gene Silencing; D019694:Hepatitis B, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology / Q000379:methods; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D004273:DNA, Neoplasm