Mo1534 Association Between Telomere Length and Risk of Cirrhosis in Patients With Chronic Hepatitis B

Abstract

Background and Aim: To screen differentially expressed genes and MicroRNAs hoping bring us a new target spot to accurate diagnosis and effective therapy in gene and MicroRNA level of alcoholic liver disease(ALD).Methods: The total RNA of peripheral blood was extracted from four groups of three subjects.And all patients signed the informed consents. Microarrays were utilized to detect differentially expressed genes and MicroRNAs. According to gene values, significance level (p values) and false discovery rate with a random variance model, combining the GO and KEGG database, node genes and key MicroRNAs in network were obtained and analyzed.Results: A total of 878 differentially expressed genes and 26 MicroRNAs were discovered. Not all of these genes have biological effects on the development of ALD. By combining the gene ontology (GO) database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, 16 significantly different pathways were found, where 31 corresponding genes participated in.Calculating betweenness centrality of each gene in network, which can describe the degree of importance of the nodes in the whole net. In co-expression network of genes, the node genes modulating the network were ACSF3, FZD5, LOC727987 and C1orf222. And in MicroRNA-Gene network the key MicroRNAs were hsa-miR-570, hsa-miR-122, hsa-miR-34b, hsa-miR-29c, hsa-miR-922 and hsa-miR-185 they negatively regulated about 79 genes locate their downstream.Conclusions: In the course of the ALD, we found 4 differentially expressed node genes in network and analyzed Acyl-coenzyme A synthetase-3 (ACSF3) , the maximal betweenness centrality in the entire gene-modulating network was 0.102935, indicating its controlling capability and significance level. Continuous up-regulation of ACSF3 maintains transcriptional activation and subsequently strengthens the binding of ACSF3 to thioester and CoA to activate fatty acids, which results in the irreversible advancement of ALD from hepatitis to cirrhosis. The gene values of Frizzled-5(FZD5) in alcoholic hepatitis and cirrhosis were clearly downregulated. The second highest value of betweenness centrality in the entire gene-modulating network was 0.087. A possible mechanism may be that continuous down-regulation of FZD5 during advancement of alcoholic hepatitis to cirrhosis decreased gene activities and syntheses of multi-transmembrane transport proteins. This reduced the number of β-catenin molecules in hepatocytes and therefore promoted hepatocyte apoptosis. The other two genes' functions were unknown. And the 6 key MicroRNAs perhaps controlled numerous biology functions such as immune response, activity of cancer gene, inflammatory mediated response, cell cycle, glutathione metabolism. Maybe the discovery will provide valuable directions to diagnosis and treatment of ALD.