The interaction between microRNA-152 and DNA methyltransferase-1 as an epigenetic prognostic biomarker in HCV-induced liver cirrhosis and HCC patients

Theodor Bilharz Research Institute

Bibliographic Information

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

Journal: Cancer Gene Therapy

Publisher: Springer Nature

Publication Date: 18 July 2019

Volume / Issue: Volume 27 / Issue 6

Pages: 486–497

ISSN: 9291903

DOI: 10.1038/s41417-019-0123-9

Scopus: View on Scopus

PubMed: 31316135

Document Type: Retracted

Authors and Affiliations

El-Araby R.E., Assistant Researcher of Molecular Biology, Central Lab, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt; Khalifa M.A., Assistant Prof. of Molecular Biology, Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt; Zoheiry M.M., Prof. of Clinical pathology (Immunology), Immunology Research Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt; Zahran M.Y., Prof. of Hematology, Clinical Laboratory, Research Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt; Rady M.I., Prof. of Cytochemistry and Histochemistry, Zoology Department, Faculty of Science, Al-Azhar University, Cairo, Egypt; Ibrahim R.A., Prof. of Hepatoastroenterology, Hepatoastroenterology Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt; El-Talkawy M.D., Prof. of Hepatoastroenterology, Hepatoastroenterology Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt; Essawy F.M., Prof. of Hematology, Clinical Laboratory, Research Department, Theodor Bilharz Research Institute (TBRI), Ministry of Scientific Research, Gizah, Egypt

Abstract

The necessity for early detection and hence improving the outcome of treatment of hepatocellular carcinoma (HCC) is critical especially in Hepatitis C virus (HCV)-Genotype 4 induced cases. In our current work, we examined the miRNA-152 and DNMT-1 expression in chronic liver disease (CLD) due to HCV genotype 4 infection with/without cirrhosis and HCC patients as an attempt to evaluate the potential benefits of these new circulating, noninvasive, prognostic, epigenetic markers for liver cirrhosis and carcinogenesis of Egyptian patients. Eighty subjects were included in this study, divided into two groups; group I (40 patients) were classified into subgroup Ia (CLD without cirrhosis, n = 18) and subgroup Ib (CLD with cirrhosis, n = 22), group II (CLD patients with HCC, n = 20), and control (Healthy volunteer, n = 20). The expression of miRNA-152 and DNMT-1 genes were analyzed using Real-Time PCR. MiRNA-152 showed a persistent and significant downregulation in all diseased groups, which was in consistence with the progression of the disease toward the HCC stage. DNMT-1 showed upregulation in all diseased groups when compared to control and subgroup Ia. The miRNA-152 was shown to correlate inversely with DNMT-1 in subgroup Ia, Ib and group II (r = −0.557, p < 0.01), (r = −0.850, p < 0.001) and (r = −0.544, p < 0.02) respectively. In addition, miRNA-152 and DNMT-1 showed a diagnostic ability to discriminate between cases of cirrhosis and HCC against CLD without cirrhosis (p < 0.01), while DNMT-1 did not, except between HCC and cirrhotic cases. Furthermore, both genes can be considered as predictor and prognostic parameters for cirrhosis (OR = 1.041, p = 0.043) and (OR = 1.039, p = 0.04) respectively, while miRNA-152 alone is proved as a prognostic marker for HCC (OR = 1.003, p = 0.044). Finally, the persistent reverse correlation between miRNA-152 with DNMT-1 prompts their use as noninvasive prognostic biomarkers for HCV induced liver cirrhosis and HCC in HCV Genotype 4 patients. © 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.

Keywords

Adolescent; Adult; Biomarkers, Tumor; Carcinoma, Hepatocellular; DNA (Cytosine-5-)-Methyltransferase 1; Epigenesis, Genetic; Female; Hepacivirus; Hepatitis C, Chronic; Humans; Liver Cirrhosis; Liver Neoplasms; Male; MicroRNAs; Middle Aged; Prognosis; Young Adult; ataxin 1; calcium calmodulir dependent protein kinase II alpha; colony stimulating factor 1; DNA (cytosine 5) methyltransferase 1; endothelial pas domain protein 1; glutathione transferase P1; homeobox c8; homeodomain protein; inhibin B; microRNA; microRNA 152; mitogen activated protein kinase 9; Rho guanine nucleotide exchange factor; transcription factor E2F3; unclassified drug; uvomorulin; virus RNA; DNMT1 protein, human; MIRN152 microRNA, human; tumor marker; Article; bioinformatics; cancer growth; cancer patient; cancer prognosis; chronic liver disease; comparative study; controlled study; down regulation; epigenetics; gene expression; gene targeting; hepatitis C; Hepatitis C virus genotype 4; human; liver carcinogenesis; liver cell carcinoma; major clinical study; predictive value; priority journal; protein RNA binding; real time polymerase chain reaction; sensitivity and specificity; upregulation; chronic hepatitis C; genetic epigenesis; genetics; isolation and purification; liver tumor; metabolism; pathology; virology

Citation Information

Scopus Citations: 12

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