GENETIC VARIANTS IN MYELOPEROXIDASE AND CATALASE PROMOTERS CONFER SUSCEPTIBILITY TO HEPATOCELLULAR CARCINOMA OCCURRENCE IN PATIENTS WITH HCV-RELATED CIRRHOSIS

Journal of Hepatology(2011)

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Abstract
POSTERSdetection of new biomarkers for Hepatocellular carcinoma (HCC) is highly needed.We focused on Natural antisense transcripts (NATs), which constitute a class of non-coding RNAs that emerged as important regulators of gene expression.We analyzed NATs expression of HCC to find a novel molecular marker using custom microarray.Methods: 29 patients with HCC were investigated; Hepatitis B virus (HBV) and Hepatitis C virus (HCV)-free HCC (8 cases), HBVassociated HCC (4 cases), HCV-associated HCC (16 cases), and HBV and HCV-associated HCC (1 case).Total RNAs isolated from HCC tissues and corresponding non-cancerous liver tissues from surgically resected samples were subjected to expression analysis using a custom-microarray containing human sense/antisense probes for ca.21,000 genes.Examination items of sense/antisense RNA were as follows i. HCC and non-cancerous liver tissue, and ii.viral infection of non-cancerous liver tissue. Results:i. 864 RNA including 285 NATs were identified as up-and downregulated in HCC tissues, compared to non-cancerous liver tissue (P < 0.001, fold change > 2.0).Hierarchical clustering of antisense RNA clearly distinguished HCC and normal liver tissue with or without viral infection.ii.We analyzed the influence of viral infection at non-cancerous liver tissue, 316 RNA including 169 NATs were identified as up-and down-regulated between historical background of viral infection (P < 0.001).Cluster analysis revealed that NATs expression was significantly correlated with the viral infection of HBV or HCV.Conclusions: Our study suggests that NATs expression of HCC is significantly different from normal liver tissue.Expression profiling of NATs is effective techniques for diagnosis of HCC carcinogenesis.In addition, analysis of the obtained NATs is helpful to understand the molecular changes in HCC progression and may lead to the identification of new targets for HCC diagnosis.
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Key words
myeloperoxidase,genetics
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