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the highest number of de genes was identified within the pbmcs of mll subjects on days 1, 3 and 10. this concurs with the overall more rapid response in pbmcs than in b-cells in gene transcription due to the presence of a large number of epstein-barr virus transcripts that is necessary for the initiation of the early immune response and the induction of immune-mediated gene transcription.
in our two initial genetic analyses, performed without using kegg pathway enrichment, we identified the up-regulated genes in mll, cd and igg stimulated pbmcs. these genes associated with immune system pathways and transcriptional regulation. the top three enriched kegg pathways included: 1-signal transduction-pathway was most significant and the most predominant; 2-immune system-related; and 3-ppar signaling pathway. other significant pathways included: 4-cytokine-cytokine receptor interaction; 5-pathways in cancer; and 6-complement and coagulation cascades. go pathway enrichment showed similar findings with immune system responses for a number of pathways for both samples; whereas for the process and response categories, mll pbmc had more enriched go terms for chemotaxis, migration, defense response, inflammatory response, and regulation of cytokine production, and cd pbmc had more enriched go terms for proteolysis, regulation of immune responses, and response to oxidative stress, etc.
our analysis of five randomized controlled trials demonstrate that the identification of de genes in response to cancer therapeutic agents might be a powerful surrogate marker for choosing the optimal adjuvant therapy. this could be easily accomplished by identifying the number of de genes that are associated with the ultimate clinical outcomes.
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