Priyanka Thummalapally

Concordance of Plasma and Tumor DNA Methylation in Egyptian Patients with Hepatocellular Carcinoma

ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth most common type of solid tumor in the world and the fourth leading cause of cancer-related mortality. The age-adjusted worldwide annual incidence is between 5.5 and 14.9 per 100,000, resulting in approximately 600,000 to 1,000,000 deaths annually. The burden of HCC has been increasing in Egypt with the incidence rate doubling in the past 10 years, and HCC is now the second highest cause of cancer incidence and mortality in men. This could be attributed to the high prevalence of HBV and HCV in Egypt, although HBV rates have declined after the introduction of the vaccine in 1992. Recent studies have shown that aberrant DNA methylation may play an important role in hepatocarcinogenesis. Liver biopsy is the current gold standard for detecting methylation events; however, imaging techniques often suffice for diagnostic purposes making tissue samples increasingly scarce. Large-scale epidemiological and molecular studies are needed to understand the role of methylation in carcinogenesis, so non-invasive detection techniques are urgently needed to feasibly conduct these studies. The efficacy of conducting DNA methylation studies using plasma DNA is still unknown. The objective of this study was to compare the tumor methylation profile in tumor tissue and plasma to test the concordance between the two types of samples from the same HCC patient. The methylation profile for the following tumor suppressor genes was compared: APC, FHIT, p15, p16, and E-cadherin. Twenty eight HCC cases with matching tissue and plasma DNA were recruited from the ongoing case control study in Garbiah, Egypt. Concordance between the tissue and plasma was statistically significant in all five genes: APC (P=.001), FHIT (P=.001), p15 (P=.045), p16 (P=.037), and E-cadherin (P=.0008). The average specificity was: 90%, 86%, 96%, 86%, 100%, respectively. In conclusion, plasma DNA can be reliable for testing the methylation profile in liver cancer patients. Future studies on a larger sample size should investigate methylation profile in populations with higher rates of HBV, HCV, and other risk factors.

Publications
Concordance of DNA methylation pattern in plasma and tumor DNA of Egyptian hepatocellular carcinoma patients
Epidemiologic risk factors of hepatocellular carcinoma in a rural region of Egypt

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