الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
HCV infection is one of the worldwide public health problems. Its seroprevalence has been increased to 2.8% over the last decade, corresponding to more than 185 million people infected all over the world.Development of CHC leads to progressing liver fibrosis and eventually cirrhosis, which can cause liver failure or the development of HCC.
HCC is the predominant form of primary malignancy of the liver. In many parts of the world including Egypt, it is one of the leading causes of cancer-related mortality. Despite knowing the highrisk populations for HCC development, the lack of sensitive and specific biomarkers hinders early detection of the disease at a curable stage. Therefore, the identification of new diagnostic markers for HCC becomes a top priority.
MiRNAs are small non-coding single-stranded RNAs that are 19–24 nt long. They are able to control gene expression at translational or post transcriptional level, either through degradation or blocking mRNA translation by binding to their 3’ UTRs.MiRNAs play a role in the most critical biological events such as proliferation, differentiation, metabolism, hematopoiesis, cell cycle, and apoptosis.Circulating miRNAs have received remarkable attention because they offer great advantages and good performance as novel biomarkers for cancer diagnosis and prognosis prediction.Among the large number of miRNAs, miRNA-23a has been paid special attention due to its relationship with malignancies. There are few reports about the relationship between miRNA-23a expression and the diagnosis of HCC.
The present study aimed to:
Evaluate serum miRNA-23a as a diagnostic biomarker of hepatitis C related HCC. Estimate the serum level of miRNA-23a among hepatitis C cirrhotic patients, non-cirrhotic patients, hepatitis C related HCC patients and healthy controls and comparing serum levels of miRNA-23a among the studied groups.
In order to achieve this goal, a total of 80 individuals were enrolled in this study. Twenty HCV infected patients without cirrhosis (group I), twenty HCV infected patients with cirrhosis (group II) andtwenty patients with HCV related HCC (group III). In addition to control group of twenty healthy volunteers.
Cirrhotic and HCC patients were categorized by Child-Pugh score and MELD score to assess the severity of liver disease. HCC patients were categorized by BCLC staging system, TNM staging system and Okuda score to assess staging of the tumor. Tumor characteristics were detected including tumor size, focal lesion number, site and PV invasion.
All patients were subjected to history taking regarding demographic data (age and sex) and complaints, general and local abdominal examination, routine laboratoryinvestigations (CBC, liver function testsand renal function tests), HCV antibodies, HCV viral load and AFP in addition to imaging techniques (US and triphasic CT).
Total RNA was extracted from serum samples followed by qRT-PCR. Expression of serum miRNA-23a was calculated using the comparative Ct method (2–ΔΔCT).
The results of the present study revealed that:
• The median of serum AFPlevels was 3.60, 4.15, 37.50 and 570 in the control group, CHC, cirrhotic and HCC patients, respectively. This result was statistically significant.
• The median of serum miRNA-23a levels (2-∆∆CT) was 0.84, 18.22 and 10.58 in the CHC, cirrhotic and HCC patients, respectively.This result was statistically significant.
• MiRNA-23a levelshadsensitivity of 55% and specificity of 95% at the cut-off value of >6.24,AFP levels had sensitivity of 100% and specificity of100% at the cut-off value of >9.2, combined miRNA-23a levels and AFP levels had sensitivity of 100% and specificity of100% at the cut-off value of >6.24+>9.2for discriminating HCC patients from CHC patients.
• MiRNA-23a levelshadsensitivity of 55% and specificity of65% at the cut-off value of ≤11.06, AFP levels had sensitivity of 80% and specificity of100% at the cut-off value of >80, combined miRNA-23a levels and AFP levels had sensitivity of 80% and specificity of100% at the cut-off value of ≤11.06+>80 for discriminating HCC patients from cirrhotic patients.
• MiRNA-23a levelshadsensitivity of 90% and specificity of 70% at the cut-off value of >1.76, AFP levels had sensitivity of 60% and specificity of 70% at the cut-off value of ≤50, combined miRNA-23a levels and AFP levels had sensitivity of 80% and specificity of 70% at the cut-off value of >1.76+≤50 for discriminating metastatic from non-metastatic HCC patients.
It can be concluded from the present study that:
• Serum AFP levelsweresignificantly higher in cirrhotic and HCC patients compared to control group and CHC patients. They were also significantly higher in HCC patients than cirrhotic patients. On the other hand, there was no significant difference between CHC patients and control group.
• Serum miRNA-23a levels (2-∆∆Ct) were significantly higher in cirrhotic and HCC patients compared to CHC patients. On the other hand, no significant difference was noted between cirrhotic and HCC patients.
• MiRNA-23a levels had lower sensitivity and specificity than AFP in discriminating HCC patients from both CHC and cirrhotic patients.
• MiRNA-23a levels had higher sensitivity and specificity than AFP in discriminating metastatic from non-metastatic HCC patients. However, this result was not statistically significant.
• MiRNA-23a cannot be used as a single biomarker for diagnosis of HCV related HCC patients.
from the results of the present study, the following recommendationsare suggested:
• Further studies are required on a largescale to determine the role of miRNA-23a as a diagnostic tool in early detection of HCC.
• Further studies are necessary on a large scale to determine the role of miRNA-23a in the prediction of metastasis in HCC patients.
• Further studies are needed for discovery and validation of other miRNAs as possible