Epigenetic and MicroRNA signatures as predictive biomarkers in HCV genotype 4-Induced liver cirrhosis and HCC

Theodor Bilharz Research Institute

Bibliographic Information

Authors: El-Araby R.E.; Khalifa M.A.; Zoheiry M.M.; Zahran M.Y.; Essawy F.M.; Rady M.I.; Ibrahim R.A.; El-Talkawy M.D.; Gad A.

Journal: Molecular Biology Reports

Publisher: Springer Science and Business Media B.V.

Publication Date: 2 February 2026

Volume / Issue: Volume 53 / Issue 1

Article No.: 347

ISSN: 3014851

DOI: 10.1007/s11033-025-11323-3

Scopus: View on Scopus

PubMed: 41627584

Document Type: Article

Authors and Affiliations

El-Araby R.E., Central Lab, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Giza, Egypt, Division of Oral Biology, Tufts University School of Dental Medicine, Boston, 02111, MA, United States; Khalifa M.A., Bioinformatics and Molecular Biology Unit, Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt; Zoheiry M.M., Immunology Research Department, Theodor Bilharz Research Institute (TBRI) Ministry of Scientific Research, Giza, Egypt; Zahran M.Y., Hematology lab, Clinical Laboratory Research Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Giza, Egypt; Essawy F.M., Hematology lab, Clinical Laboratory Research Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Giza, Egypt; Rady M.I., Cytochemistry and Histochemistry Lab, Zoology Department Faculty of Science, Al-Azhar University, Cairo, Egypt; Ibrahim R.A., Hepatoastroenterology Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt; El-Talkawy M.D., Hepatoastroenterology Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt; Gad A., Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, 6 A Aswan Square, El Mohandeseen, Cairo, Egypt

Abstract

Introduction: Hepatocellular carcinoma (HCC) and chronic liver disease (CLD) are mostly linked to hepatitis C virus (HCV) infection, especially genotype 4. The advancement of liver cancer is significantly influenced by epigenetic mechanisms, such as DNA methylation and microRNA regulation. Aim of the study: This study aimed to assess the expression of two tumor suppressor genes in patients infected with HCV genotype 4: glutathione S-transferase pi 1 (GSTP1) and E-cadherin 1 (CDH1). It also sought to investigate the regulatory interactions among these genes, microRNA152 (miRNA152), and DNA methyltransferase 1 (DNMT1) to assess their potential as biomarkers for hepatocellular carcinoma (HCC) development. Methods: Quantitative real-time PCR was done to evaluate the gene expression levels of GSTP1, CDH1, miRNA152, and DNMT1 in CLD and HCC patients infected with HCV genotype 4. Correlation analyses were used to examine regulatory linkage. Results: The results indicated a substantial inverse correlation between DNMT1 and miRNA152. Furthermore, DNMT1 expression exhibited a negative association with both GSTP1 and CDH1, while GSTP1 and CDH1 had a positive correlation. The results indicate that DNMT1 and miRNA152 govern the epigenetic inactivation of tumor suppressor genes. Conclusion: In individuals with HCV genotype 4, the interplay of miRNA152, DNMT1, GSTP1, and CDH1 may contribute to the pathogenesis of HCC. These indicators demonstrate potential roles as therapeutic targets and noninvasive prognostic biomarkers for HCV-related liver disease. © The Author(s), under exclusive licence to Springer Nature B.V. 2026.

Keywords

CDH1; Cirrhosis; CLD; DNMT1; Genotype 4; GSTP1; HCC; HCV; MiRNA152; Adult; Antigens, CD; Biomarkers, Tumor; Cadherins; Carcinoma, Hepatocellular; DNA (Cytosine-5-)-Methyltransferase 1; DNA Methylation; Epigenesis, Genetic; Female; Gene Expression Regulation, Neoplastic; Genotype; Glutathione S-Transferase pi; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms; Male; MicroRNAs; Middle Aged; alanine aminotransferase; alpha fetoprotein; aspartate aminotransferase; biological marker; DNA (cytosine 5) methyltransferase 1; microRNA; cadherin; CDH1 protein, human; DNMT1 protein, human; glutathione transferase P1; GSTP1 protein, human; leukocyte antigen; tumor marker; Article; autoimmune hepatitis; chronic liver disease; clinical examination; computer assisted tomography; controlled study; diagnostic test accuracy study; enzyme linked immunosorbent assay; epithelial mesenchymal transition; genotyping; Hepatitis C virus genotype 4; housekeeping gene; human; hypoalbuminemia; hypoprothrombinemia; KEGG; liver carcinogenesis; liver cell carcinoma; nonalcoholic steatohepatitis; nuclear magnetic resonance imaging; pathogenesis; prothrombin time; real time polymerase chain reaction; risk assessment; schistosomiasis; sensitivity and specificity; tumor suppressor gene; chronic hepatitis C; gene expression regulation; genetic epigenesis; genetics; liver tumor; metabolism; virology

Citation Information

Scopus Citations: 0

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