الفهرس 
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Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cause of cancer and the third leading cause of cancer-related deaths. Major risk factors for HCC include HCV, HBV, chronic alcohol consumption, and NAFLD. HCC originates from CSCs that are present in adult hepatic tissue.
Cancer stem cell (CSC) identification typically relies on the use of cell surface markers called LCSCs. These LCSC markers include CD133, EpCAM, CD44, and ALDH, which have great potential in the diagnosis, therapy, and prognosis of liver cancer. MicroRNAs have proven to be able to regulate different molecular pathways and checkpoints of the cell division cycle. Thus, microRNAs may play an important role in HCC development. Let-7 miRNA was demonstrated to be downexpressed in the liver tissue of HCC patients. Let-7 miRNA targets oncogenes and genes important for HCC initiation and progression, including Myc and β-catenin.
This study was conducted to investigate the potential role of LCSC markers and let-7 miRNA and the related target genes (c-Myc and β-catenin) in the pathological development and progression of HCV-induced HCC patients.
Our study was conducted at TBRI on 100 subjects recruited in the outpatient clinics and inpatient wards of the Hepato-Gastroenterology Department. They were divided into four groups: (1) 25 patients with CHC-HCC; (2) 25 CHC-cirrhotic patients; (3) 25 CHC-non-cirrhotic patients; and (4) 25 healthy controls. All patients were subjected to a full history taking, a detailed clinical examination, laboratory and radiological investigations, as well as flowcytometric analysis of LCSC markers (CD133, CD44, EpCAM, and ALDH), let-7 miRNA expression analysis by real-time PCR, and c-Myc and β-catenin detection by real-time PCR.
Our study showed that the levels of CD133, CD44, EpCAM, and ALDH presented a statistically significant difference between groups, with the lowest level found in the control group and the highest level in the HCC group. Our study also showed that the level of let-7 miRNA presented a statistically significant difference between groups, with the lowest level found in the HCC group and the highest level in the control group. This study also demonstrated that the circulating levels of c-Myc and β-catenin showed a significant increase in the HCC group compared to other study groups.
In conclusion, Let-7 miRNA, its related target genes (c-myc and β-catenin), and LCSC markers (CD133, CD44, EpCAM, and ALDH) could be promising biomarkers to estimate the disease progression rate from HCV-non-cirrhotic liver to cirrhotic liver, and finally to HCC.