الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the fifth most common cancer worldwide. The prognosis of HCC is mostly poor, because of detection at an advanced, non-resectable stage. Current diagnosis of HCC relies on clinical information, hepatic ultrasonography and measurement of serum alpha-fetoprotein (AFP) at 6-12 month intervals but neither of these is adequate for detecting very small (< 2 cm) HCC tumors. The sensitivity of AFP is low particularly in detection of early-stage HCC. Therefore, there is an urgent need to identify novel biomarkers with high efficacy for early detection and therapeutic monitoring of HCC.
MicroRNAs are conserved small non-coding RNA molecules, about 21–25 nucleotides in length that inhibit protein synthesis by protein-coding genes at the post-transcriptional level leading gene silencing. Several miRNAs have been found to have links with several types of cancer and are referred to as ”oncomiRs”. Although miRNAs are endogenous, they are also found in body fluids including serum and plasma that make them useful potential markers for detection of cancer.
Among the large number of miRNAs, miR-143 has been paid special attention due to its relationship with malignancies. There are few reports about the relationship between miR-143 expression and the diagnosis of HCC, so, the aim of the work was to study serum miR-143-expression level in patients with HCV-related HCC.
To achieve this goal, the study was conducted on 45 patients with HCV related cirrhosis divided as follows:
30 patients with HCC as group (A) and 15 patients without HCC as group (B). In addition, group (A) was subclassfied according to BCLC classification into 10 patients with HCC stage A BCLC, 10 patients with HCC stage B BCLC and 10 patients with HCC stage D BCLC. Also, 15 age- and sex-matched healthy subjects with no evidence of liver disease were included as control group as group (C).
The diagnosis of chronic HCV infection with cirrhosis was based on positive test for HCV antibody, detectable serum HCV RNA and the diagnosis of cirrhosis was determined by clinical, biochemical and ultrasonographic evidences. The diagnosis of HCC was based on serum levels of AFP, ultrasonography and triphasic computed tomography (CT).
All the patients of group A and B were selected from the Hepatobiliary Unit of Main Alexandria University Hospital.
Patients who have the following criteria: Seropositivity for HBV infection, other causes of chronic liver diseases, chronic illness (e. g: collagen diseases, diabetes mellitus, autoimmune diseases) Cardiac, respiratory or renal diseases, chronic alcoholism and other malignancies were excluded from the study.
All patients included in the study were evaluated clinically as regards History taking and clinical examination in cirrhotic patients focused on symptoms and signs of chronic liver disease (previous upper gastrointestinal bleeding, jaundice, ascites, hepatic encephalopathy and bleeding diathesis), presence of palpable focal hepatic lesions, liver size and spleen size. Blood samples were collected from all patients on admission and from healthy subjects and the following tests were performed: CBC, serum creatinine, liver test profile [AST, ALT, serum albumin, serum bilirubin, GGT and PT], serum HCV RNA levels using real time PCR and serum AFP levels using ELISA kit. The severity of liver disease in patients with HCV-related cirrhosis with and without HCC was graded according to Child-Pugh classification. Radiological examination using ultrasonographic/ triphasic CT examination was performed for assessment of liver echopattern, liver and spleen size, presence of ascites and tumor characteristics in patients with HCC (maximum diameter, echopattern, number of nodules, extension, portal vein invasion and intrahepatic metastasis). The staging of HCC was determined according to the BCLC staging system. Total serum RNA was extracted with small RNA enrichment followed by reverse transcription real time PCR. Expression of miR-143 in the serum of all subjects was obtained using the comparative CT method (2–ΔΔCT) after normalization for the expression of Syn-cel-miR-39 as a control. Serum miR-143 expression levels were then compared in different groups.