الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma is the fifth most common malignancy in the world and the third most common cause of cancer related deaths worldwide.
The search for reliable and efficient biomarkers for a diagnostic and prognostic evaluation is still an open issue. AFP is still universally used, although several studies have repeatedly demonstrated that both the sensitivity and specificity of the marker are not high enough to justify its routine use, despite some recent attempt to rehabilitate the marker. Better performance are provided by AFP in defining the prognosis of HCC patients.
MIRNAs can act as both tumor suppressors (by binding to oncogenes and suppressing them) and oncogenes (by binding to tumor suppressor genes and suppressing them) . miR-224 is one of the most commonly overexpressed MIRNAs in hepatocellular carcinoma (HCC) tissues .
The upregulation of miR-224 starts form the precancerous stage and persists throughout HCC development .
miR-224 played a role in cell proliferation, migration, invasion, and antiapoptosis in HCC by directly binding to its gene targets, thus, miR-224might be a potential biomarker for diagnosis and prognosis of HCC .
This study included thirty five patients with hepatocellular carcinoma ( HCC ) on top of hepatitis C virus ( HCV ) related cirrhosis and twenty patients with liver cirrhosis without hepatocellular carcinoma, matched for age and sex to studied group , as control group .All patients were classified according to Child-Pugh classification into Child s classes A , B , C .
All 35 HCC patients were classified according Barcelona classification for liver cancer ( BCLC ) into 15 patients with BCLC A, 10 patients with BCLC B and 10 patients with BCLC C .
All patients were subjected to thorough clinical history and examination, laboratory assessment, abdominal ultrasonography.
MDCT abdomen was done for those with hepatitic focal lesions detected by abdominal ultrasonography for confirming the presence of HCC on top of liver cirrhosis. Serum alpha-fetoprotein and MIR -224 levels were estimated for all patients.
Interestingly, the statistical ROC curve analysis showed that miR-224 had excellent sensitivity (97.1%) , specificity (95%) and positive predictive value ( 95%) as compared to AFP ( 45%) , ( 90%) , ( 90%) respectively, and could serve as potential biomarker for diagnosis of HCC.
The area under the curve was 0.994 at cut off value 8( CT value) with p value 0.001 while for AFP it was 0.812 at cut off value 400 ng | ml with p value 0.001, indicating statistically significant difference in favour of miR-224.
We found that serum level of miR- 224 was higher in HCC patients with portal vein thrombosis, than in patients with HCC without portal vein thrombosis and this finding was statistically significant with P value 0.001.
When evaluating the ability of miR- 224 in predicting progression and prognosis of HCC, we found that the serum level of miR- 224 was increased as the tumor grade increase with its lowest level in BCLC A and its highest level in BCLC C , and these results was significant ( P value 0.001), denoting the ability of miR-224 to predict grade of HCC.
In addition we found that the serum level of miR-224 was significantly correlated with parameters of liver damage as serum bilirubin ,serum ALT and AST . The results showed that serum levels miR-224 showed significant correlation with parameters of severity of liver damage, such as ALT, AST, and bilirubin level ( P values were 0.001).
Our study showed that there is a significant difference between the mean of level miR 224 in group A ( 15 patients) before and after one month of treatment with radiofrequency ablation ( P o.oo1) , denoting the dynamic action of miR 224 in predicting response to treatment.