الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
 |  | from | 202 |  |  |
| | | from | 202 | | |
Abstract
HCC presents with widely varying biological behavioral patterns. This may stem from its diverse etiologies including different types of viruses, non-viral etiologies and environmental factors. This widely diverse natural history may reflect the underlying molecular mechanisms involved in the process of hepatocarcinogenesis complicating HCV type 4 in Egyptian patients.
The present study aimed at determining the gene expression pattern of a cohort of Egyptian HCCs complicating chronic HCV genotype 4 by the qRT-PCR technology using RT2 profiler PCR array for Human insulin signaling/ IGF1R pathway which includes primers for 84 insulin pathway related genes. Then the gene expression levels were correlated to different patient/tumor characteristics. The most frequently coregulated genes among the significantly upregulated ones were determined. Finally, canonical pathway analysis, of the present data set, using the IPA database to identify active and inactive pathways in the present cohort was performed.
Gene dysregulation was observed in HCC patients relative to the control group. Six genes namely AEBP1, AKT2, FOS, PIK3R1, PRKCI, SHC1 genes were significantly overexpressed in HCC patients. SHC1 was the most significantly overexpressed gene.
On the other hand, thirteen genes, namely ADRB3, CEBPA1, DUSP14, ERCC1, FRS3, IGF2, INS, IRS1, JUN, MTOR, PIK3R2, PPP1CA and RPS6KA1 were significantly under expressed in HCC patients relative to the control group, where PPP1CA and INS were the 2 most significantly under expressed genes.
Regarding histopathological characteristics of HCCs. GSK3A gene expression was significantly higher in low grade in comparison to high grade HCCs. NOS2 expression was significantly higher in tumors with vascular invasion in comparison to those without. Regarding giant cells, expression of GSK3A, PCK2 and UCP1 genes were significantly different between tumors with and those without giant cells. CEBPB, GPD1, HK2, IGFBP1 and PIK3R2 genes showed significant differential expression between tumors with clear cells and tumors without.
Regarding gross tumor characteristics. CEBPB and GPD1 had significantly lower expression in tumors >5cm than tumors ≤5cm in maximum dimension. The expressions of AEBP1, CFOS and LDLR were significantly higher in unifocal in comparison to multifocal tumors. According to the presence or absence of satellite nodules, significant differences were seen in the expression of AEBP1, CFOS, MAPK1, PRKCZ and UCP1 genes. INSL3 and IRS1 were significantly differentially expressed between tumors with and without gross tumor encapsulation. Tumors with gross necrosis showed significantly different expression in CAP1, GRB2, PIK3R1, PRL and TG genes relative to tumors with no gross necrosis.
Regarding patients’ demographic data. DOK1 was expressed at significantly higher levels in females as compared to males. Also, significant differences were seen in the expression of AEBP1, AKT1 and FBP1 between patients below and above 60 years of age.
RPS6KA1 was significantly under expressed