Methylation of tumour suppressor genes RUNX3, RASSF1A and E-Cadherin in HCV-related liver cirrhosis and hepatocellular carcinoma. Issue 1 (2nd January 2020)

• Record Type: Journal Article
• Authors: El-Bendary, Mahmoud; Nour, Dina; Arafa, Mona; Neamatallah, Mustafa
• Is Part Of: British journal of biomedical science. Volume 77:Issue 1(2020)
• Page Start: 35
• Page End: 40
• Publication Date: 2020-01-02
• Subjects: HCC -- HCV-related cirrhosis -- hypermethylation -- RASSF1A -- E-Cadherin -- RUNX3; Medical sciences -- Periodicals; Medical technology -- Periodicals; Biological Science Disciplines; Clinical Laboratory Techniques; Medical Laboratory Science; Anatomie pathologique; Medical sciences; Medical technology; Klinische chemie; Laboratoriumonderzoek; Periodicals; Periodicals; 616.0756; 610.07 M489L
• DOI: 10.1080/09674845.2019.1694123
• Languages: English
• ISSNs: 0967-4845

Abstract

ABSTRACT: Background : HCV infection is related to aberrant methylation of several genes. RASSF1A, E-Cadherin and RUNX3 are tumour suppressor genes that may be inactivated by hypermethylation in many tumours including hepatocellular carcinoma (HCC). We hypothesized that methylation is a diagnostic biomarker for HCC in patients with HCV-related liver cirrhosis. Methods : We recruited 207 cases of HCV-related liver cirrhosis, 193 HCC patients and 53 healthy controls. Methylation-specific polymerase chain reaction for detection of circulating hypermethylated RASSF1A, E-Cadherin and RUNX3 . Alpha fetoprotein (AFP) was measured by commercial immunoassay. Results : Significant hypermethylation of the three genes was found in the HCC group compared to both cirrhosis and healthy groups ( P < 0.001), whereas no significant difference in hypermethylation was found between cirrhosis and healthy groups ( P = 0.17, 0.50 and 0.14, respectively). No significant links were found between hypermethylated RASSF1A, E-Cadherin and RUNX3 and stages of Barcelona Clinic of Liver Cancer score ( P = 0.21, 0.63 and 0.98, respectively). No significant associations were found between AFP value and hypermethylated genes in cirrhosis and HCC groups ( P = 0.82) except with E-Cadherin in HCC ( P = 0.02). In multiple regression analysis, RASSF1A and E-Cadherin were predictors of HCC within cirrhosis cases, but only E-Cadherin was an independent risk factor for prediction of HCC in cases with low AFP ( P = 0.01). Conclusions : The presence of hypermethylated serum RASSF1A, E-Cadherin and RUNX3 is linked to HCC in patients with HCV-related cirrhosis. Only E-Cadherin is an independent risk factor for prediction of HCC with low AFP. These findings may be of diagnostic value.