Mona M Hassouna1, Mary Naguib1, Enas M Radwan2, Mohamed Abdel-Samiee3, Suzanne Estaphan4, Eman Abdelsameea3. 1. Department of Clinical and Chemical Pathology, National Liver Institute, Menoufia University, Shebeen El-Kom, Egypt. 2. Department of Clinical pathology, National Cancer Institute, Cairo University, Cairo, Egypt. 3. Hepatology and Gastroenterology, National Liver Institute, Clinical Pathology, Menoufia University, Shebeen El-Kom, Egypt. 4. Department of Physiology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Abstract
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health concern in many countries including Egypt. The alteration in DNA methylation that was observed in HCC patients suggests a possible role of DNA methyltransferases (DNMTs) in the disease pathogenesis in addition to potential role as a disease biomarker. AIM: To study the change in DNMTs expression in chronic HCV infected patients as potential non- invasive biomarker for diagnosis of hepatocellular carcinoma. METHODS: 26 patients with HCC, 45 patients with liver cirrhosis, 20 chronic HCV patients and 20 apparently healthy individuals as a control group were enrolled in this study. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed for all study participants. RESULTS: A significant difference in DNMTs expression was observed among the studied groups. Receiver operating characteristics (ROC) curve analysis revealed that with a cutoff value of 3.16 for DNMT 3A expression, sensitivity and specificity were 80.8 and 95.6% respectively and area under curve (AUC) was 0.958, p < 0.001 for discriminating hepatocellular carcinoma among post hepatitis C cirrhotic patients. Besides DNMT 3B relative expression cutoff value of 3.10 showed 84.6% sensitivity and 77.8% specificity and AUC was 0.888, p < 0.001. On the other hand, cutoff value 0.65 for DNMT1 relative expression showed 92.3% sensitivity and 44.4% specificity and AUC was 0.72, p= 0.002. DNMT1, DNMT 3A and DNMT 3B have significant positive correlation with the level of AFP (p-value = 0.003, 0.004 and 0.008 respectively). The relative expression of DNMT3B was significantly correlated to focal lesion size (p-value = 0.015). High DNMTs expression was significantly associated with the presence of multiple focal lesions but not with the Child Pugh grade (p> 0.05). CONCLUSION: The mRNA levels of DNMTs could be a potential biomarker for early detection of HCC development.<br />.
BACKGROUND:Hepatocellular carcinoma (HCC) is a major health concern in many countries including Egypt. The alteration in DNA methylation that was observed in HCC patients suggests a possible role of DNA methyltransferases (DNMTs) in the disease pathogenesis in addition to potential role as a disease biomarker. AIM: To study the change in DNMTs expression in chronic HCV infectedpatients as potential non- invasive biomarker for diagnosis of hepatocellular carcinoma. METHODS: 26 patients with HCC, 45 patients with liver cirrhosis, 20 chronic HCV patients and 20 apparently healthy individuals as a control group were enrolled in this study. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was performed for all study participants. RESULTS: A significant difference in DNMTs expression was observed among the studied groups. Receiver operating characteristics (ROC) curve analysis revealed that with a cutoff value of 3.16 for DNMT 3A expression, sensitivity and specificity were 80.8 and 95.6% respectively and area under curve (AUC) was 0.958, p < 0.001 for discriminating hepatocellular carcinoma among post hepatitis C cirrhoticpatients. Besides DNMT 3B relative expression cutoff value of 3.10 showed 84.6% sensitivity and 77.8% specificity and AUC was 0.888, p < 0.001. On the other hand, cutoff value 0.65 for DNMT1 relative expression showed 92.3% sensitivity and 44.4% specificity and AUC was 0.72, p= 0.002. DNMT1, DNMT 3A and DNMT 3B have significant positive correlation with the level of AFP (p-value = 0.003, 0.004 and 0.008 respectively). The relative expression of DNMT3B was significantly correlated to focal lesion size (p-value = 0.015). High DNMTs expression was significantly associated with the presence of multiple focal lesions but not with the Child Pugh grade (p> 0.05). CONCLUSION: The mRNA levels of DNMTs could be a potential biomarker for early detection of HCC development.<br />.
Entities:
Keywords:
DNA Methylation; DNA methlyltransferase; Epigenetics; HCV; Hepatocellular carcinoma
Authors: Mary Naguib; Mohamed M Helwa; Mohammed M Soliman; Mohamed Abdel-Samiee; Ashraf M Eljaky; Osama Hammam; Hassan Zaghla; Eman Abdelsameea Journal: Asian Pac J Cancer Prev Date: 2020-04-01