http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
( Hoda El Aggan ),( Sabah Mahmoud ),( Nevine El Deeb ),( Amany Elyamany ),( Manar Attia ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1
Aims: Hepatitis C virus (HCV) is a major risk of hepatocellular carcinoma (HCC), however, the molecular mechanism of HCV-related hepatocarcinogenesis is still unclear. The polycistronic microRNA (miR)-17~92 cluster, designated also as “OncomiR-1”, plays a role in tumorigenesis and is transactivated by c-MYC oncogene. The cluster negatively regulates phosphatase and tensin homolog (PTEN) and activates nuclear factor-kappa B (NF-κB). The present study was designed to evaluate plasma levels of miR-17 host gene (MIR17HG) protein, encoded by miR-17~92 cluster host gene, in patients with HCV-related HCC in relation to tumor c-MYC, PTEN and NF-κB expression. Methods: Forty five patients with chronic HCV infection [18 patients with chronic hepatitis C (CHC), 12 patients with cirrhosis and 18 patients with HCC] and 15 healthy subjects were enrolled in the study. The HCC stage was determined according to the Barcelona Clinic Liver Cancer (BCLC) staging system and Cancer of the Liver Italian Program (CLIP). Quantitative measurement of plasma MIR17HG protein levels was performed using an enzyme-linked immunosorbant assay kit. The HCC histologic grade was assessed according to Edmonson and Steiner scoring system. Immunohistochemical staining of liver specimens was done using anti-human antibodies against c-MYC, PTEN and NF-kB and was scored semiquatitatively. Results: Plasma MIR17HG protein levels showed significant increases in CHC and cirrhotic patients with and without HCC compared with healthy subjects and in patients with HCC compared with those without HCC (P < 0.001). By plotting ROC curve, the sensitivity and specificity of plasma MIR17HG protein levels in detecting HCC were 100% and 93.3% respectively at a cut-off level of 257.25 pg/ml [AUC = 0.996]. The HCC tissues showed a significant increase in c-MYC, and NF-kB expression and a significant decrease in PTEN expression compared with CHC, cirrhotic and surrounding non-neoplastic liver tissues (P < 0.05). The plasma MIR17HG protein levels were positively correlated with tumor size (P = 0.001), stage (P = 0.001) and HCC histological grade (P = 0.002) and c-MYC (P = 0.001) and NF-kB expression (P = 0.015) and were inversely correlated with PTEN expression (P = 0.001). Conclusions: Activation of miR-17~92 cluster induced by c-MYC may play an important role in the development and progression of HCV-related HCC, possibly, through inhibition of PTEN and activation of NF-kB and could provide a potential therapeutic target for HCC. Circulating MIR17HG protein could be a useful non-invasive biomarker for the detection of HCC in chronic HCV infection.