Abstract 2163: Global gene expression profiles of the Egyptian hepatocellular carcinoma associated with HCV-Genotype-4

Abstract

Abstract Background: Hepatocellular carcinoma (HCC) is a preventable disease rather than a curable one, since there is no well-documented effective treatment modality until now, making the molecular study of this disease mandatory. Methods: Forty cases of HCV genotype 4-associated HCC patients from Egypt were studied for gene expression profile by 41 K c-DNA microarray. Result: Out of the 41,000 genes, 958 were differentially expressed; 503 were up regulated (58 genes are involved in 65 different pathways) and 455 were down regulated (49 genes are involved in 59 different pathways). Only 19 pathways were specifically up regulated by 27 genes (ABCB10, ABCG2, RXRA, PRKAB2, IKBKG, ELOVL2, RAF1, ATP6V1A, FLJ21865, GUSB, IL7, EPO, CD1B, FGFR1, PDPK1, KPS6KB1, NOTCH4, CDK7, MNAT1, PRKACB, RXRA, PRKACB, ACCN1, RPS6KB1, BMP8A, SMAD6, CYCLIN E2) and 13 pathways are specifically down regulated by 19 genes (ARHGEF2,WASL, BACE1, A2M, PPP3CA, SLC1A, ITGAV, NRXN2, NCAM1, PER1, PIGX, ST3GAL2, ST3GAL4, DGKQ, ATG5, ENPEP, POLR2B, LTA). Sixty seven genes showed significant difference in their expression between HCC cases with and without cirrhosis. Confirmation of array data by RT-PCR was performed on a subset of genes (PPP3CA [75%], ATG-5 [85%], BACE [62%] which showed down regulation and ABCG2 [90%], RXRA [80%], ELOVL2 [65%], CXR3 [80%]) which showed up regulation. Conclusion: This is the first study on the global gene expression profile in Egyptian HCC patients associated with HCV-Genotype-4 using the cDNA microarray. The identified genes could provide a panel of new prognostic and diagnostic markers for HCV- associated HCC. Also, our data identified some genes which are related to hepatic encephalopathy like ACCN1, BACE1, apoB, GABA-A AND ATG5 which could play an important role in the cross talk between liver and brain. They could also be used to identify candidate genes for molecular target therapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2163.