الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
HCC is a widely distributed cancer and a major cause of cancer related mortality. It is caused by different environmental factors such as (HCV) or (HBV) viral infections, alcohol consumption, smoking, and diabetes mellitus, other hereditary diseases but genetic factors play a major role in progression of these diseases to HCC. DNA damage usually accompanies chronic infections and DNA repair system plays an essential role in prevention of accumulation of DNA mutations hence decreasing chance of hepatocarcinogenesis.A high Reversion-inducing-cysteine-rich protein with Kazal motifs (RECK) gene is a relatively new discovered gene with important implications for cancer research and has become a central topic in the discussion of new diagnostic biomarkers detecting early stages of cancer and the possibility of developing prolonged survival indicators for cancer patient. The RECK protein does not have a cytotoxic effect on tumor cells. A high RECK mRNA expression has been considered as a tumor suppressor gene in HCC tumor tissues from patients with better survival and less invasive clinicopathologic features. RECK gene acts as a suppressor gene which inhibits angiogenesis, invasion and metastasis DNA methylation changes are frequently found in human cancers. Hypomethylation of oncogenes can result in aberrant activation, and hypermethylation of suppressor genes can lead to silencing Multivariate analysis showed that the methylation status of the RECK gene was the only independent prognostic factor affecting overall survival of cancer patients (p = 0.037). This suggests that RECK is a promising biomarker in the early detection of cancer. The current study aimed to evaluate methylation status of RECK gene promoter in different stages of HCC on top of HCV infection and to investigate the possible relationship to the clinical criteria of HCC. The current study included 50 persons and they were divided into group 1: 10 patients with HCC stage A (single or up to 3 nodules, each<3cm).group 2: 10 patients with HCC stage B (large multinodular).group 3: 10 patients with HCC stage C (vascular invasion).Control groups were divided into two groups:Control group (A): 10 patients infected with HCV without HCC.Control group (B): 10 healthy persons without HCV.RECK gene promoter hyper-methylation is linked to HCV related HCC. Moreover, different degree of RECK gene promoter methylation (partial methylated and hyper-methylated forms) is associated with chronic HCV [genotype-4] infection which could prove its pathogenic role as a risk factor for hepato-carcinogenesis. Further researches on a larger number of patients are recommended. Also we found that the frequency of RECK hypermethylation was higher in HCC samples than in non-tumor samples . Hypermethylation of RECK gene was associated with lymph node metastasis and vascular invasion. Thus, downregulation of RECK gene by methylation leading to more tumour aggressiveness proving the role of RECK gene as tumour suppressor for HCC.