Abstract
cellular mechanisms and utilization of high-throughput functional genomics analysis. We investigated the genomic and functional characteristics of liver tissues in chronic hepatitis B (CHB) patients. Methods: Liver biopsies were utilized in 139 CHB patients and pathological Scheuer stages were defined among the specimens. The Affymetrix GeneChipTM Human Genome U133A microarray, used to establish the gene expression signature. Genomic profiles and data analysis were obtained through GeneSpring 10 software. Gene Ontology annotations were used to assess functional characterization. Results: 1. Samples were clustered according to Scheuer’s stage groups (S0–S4: n =48; 23; 37; 17; 14). 2. Cluster analysis led to result supporting the conclusion that the gene expression profiles robustly reflected the Scheuer’s classification. 3. An Welch t-test, in order to find the significant differentially expressed genes between S1–4 groups and S0 group, generated a list of 1,451 genes (P-value = 5×10−6). Group-based comparisons for S4 versus S0, it showed over 2 times up-regulated genes (n =174) and down-regulated genes (n =45). Among up-regulated 174 genes, genes with function in the structural molecular activity were most frequently up-regulated (n =58, 26.7%), and genes involved in signal transduction (n =26, 12.0%) or cell adhesion (n =24, 11.1%) were less commonly upregulated respectively. (4) A detailed analysis of the pathways related to differentially expressed genes was characterized involved in activation of 164 signaling pathways (P ≤ 0.05) and 15 signaling pathways (P ≤ 0.001). Conclusions: Through analysis of gene expression profiles of liver tissues in CHB patients, we have identified a set of genes and signaling pathways defining a molecular portrait of fibrogenesis. The present study described differentially expressed genes throughout all stages of HBV-related fibrosis and nearly 50% genes of twice up-regulated with functions in structural molecular activity, signal transduction, and cell adhesion. Furthermore, many signaling pathways are activated during the transition to cirrhosis, including inflammatory/immune responses, cell proliferation, and apoptosis pathways.
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