الفهرس 
ACKNOWLEDGEMENT
HCC Risk factorsOnly 14 pages are availabe for public view
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Abstract
Liver cirrhosis and its complications are major clinical problems that carry a considerable risk of disability and death, So prevention and treatment of complications is a keystone for the clinical care of liver patients.
Currently, accurate diagnosis of frank HCC is achieved by radiologic imaging. In inconclusive cases, the gold standard remains histopathology. More difficult in the proper diagnosis of small HCC which frequently doesn’t present with typical vascular patterns in imaging tests and acquisition of reliable histopathological specimen often require repetitive biopsies and pathological interpretation is demanding.Therefore, one of the most challenging aspects is the detection of premalignant lesions by epigenetics.
The development of new biomarkers for early HCC detection is an important area of HCC research and has the potential to improve the overall survival rates,Abnormal gene expression in cancerous cells often occur as a result of genetic mutation, but a recent study suggested that aberrant DNA methylation as an alternative mechanism of tumor pathogenesis and could be potential biomarker for early detection.
The present study aimed to: Evaluate the role of hypermethylation of APC, P14, E-Cadherin genes in the pathogenesis of HCV related HCC cases and Assess the methylation frequency of APC, P14, E-Cadherin genes in HCC with HCV related liver cirrhosis.
The study involved 50 participants recorded on the period from March 2015 to september 2016 and were classified into 3 groups:
A- Patients with HCV related liver cirrhosis (20 patients), B- patients with HCC on top of HCV related cirrhosis (20 patients), C- normal persons (control group) (10 persons), All participants were subjected to the following:
History taking and clinical examination.
Imaging Modalities. Laboratory investigations.
Epigentic study:
Study of the unmethylated genes,then artificial DNA methylation for studying the methylation frequency, PCR analysis for E-cadherin, APC, P14 genes, Methylated DNA quantification using epigenetic ELISA kit.
In this study, the frequency of methylated genes after induction of artificial methylation among participants of the 3 study groups: E-cadherin gene was methylated among 7 patients (35%) with LC, 11 patients (55%) with LC with HCC while among 3 persons (30%) in the control group. P14 gene was methylated among 9 patients (45%) with LC with HCC while no patients with LC and no persons in the healthy control group had methylated P14 gene. APC gene was methylated among 5 patients (25%) with LC, 14 patients (70%) with LC with HCC while among 2 persons (20%) in the control group.
DNA quantification using ELISA epigenetic kits was done and showd that The mean level and range of methylated DNA were significantly higher among patients with LC with HCC group in comparison to those with LC and healthy persons in the control group (P-value < 0.001 for each). On the other hand there
was no statistically significant difference between patients with LC and persons of the control group regarding the level of DNA methylation.
The sensitivity, specificity, positive and negative predictive values and accuracy of ELISA epigenetics for prediction of HCC. When the ELISA epigenetics was used as a biomarker for prediction of HCC among patients with LC at cutoff value >2.9, the sensitivity, specificity, positive and negative predictive values and accuracy were 95%, 90%, 90.5%, 94.7% and 92.5%.
While in comparison to those in the healthy control group at cutoff value >2.3, the sensitivity, specificity, positive and negative predictive values and accuracy were 80%, 90%, 94.7%, 66.7% and 85%
Univariate and multivariate analysis (logistic regression) to assess the significance of methylation of the 3 investigated genes in the prediction of HCC among patients with LC was done: Regarding P14 gene univariate and multivariate analysis of the methylation of this gene were associated with odds ratios of 33.9 and 21.4 respectively with significant risk of HCC among patients with LC(P- value<0.05). Similarly, univariate and multivariate analysis of the methylation of APC gene were associated with odds ratios of 7 and 7.8 respectively with significant risk of HCC among patients with LC (P-value<0.01). on the other hand univariate and multivariate analysis of the methylation of E-cad gene were associated with odds ratio of 2.26 and2.11 respectively with non significant risk of HCC among patients with LC.
The sensitivity, specificity, positive and negative predictive values and accuracy of the methylation Using the three methylated genes together as a biomarker for detection of HCC were 90%, 60%, 69.2, 85.7 and 75% respectively.