Franny Jongbloed

60 CHAPTER 3 Table 1. (continued) Canonical Pathway Pathway classification P- value Genes Ratio Z-score Phospholipase C Signaling Intracellular and second messenger signaling 9.09 E -03 13/240 (5.4%) -1.155 Estrogen-Dependent Breast Cancer Signaling Cancer 1.50 E -04 9/77 (11.7%) -1.134 EGF Signaling Growth Factor Signaling; cellular growth and proliferation and development 1.73 E -03 7/68 (10.3%) -1.134 Androgen Signaling Nuclear receptor signaling 2.19 E -03 9/111 (8.1%) -1.134 Cholecystokinin/Gastrin-mediated Signaling Neurotransmitters and other nervous system signaling 2.87 E -07 14/101 (13.9%) -1.069 CXCR4 Signaling Cytokine signaling; cellular immune response 2.30 E -05 15/165 (9.1%) -1.069 Gaq Signaling Intracellular and second messenger signaling 6.96 E -05 14/161 (8.7%) -1.069 Production of Nitric Oxide and Reactive Oxygen Species in Macrophages Cellular immune response 4.88 E -04 14/194 (7.2%) -1.069 14-3-3-mediated Signaling Cell Cycle Regulation; Apoptosis 2.00 E -03 10/131 (7.6%) -1.000 P70S6K Signaling Cellular stress and injury; cellular growth and proliferation and development 2.11 E -03 10/132 (7.6%) -1.000 HGF Signaling Growth Factor Signaling; cellular growth and proliferation and development; organismal growth and development 2.79 E -03 9/115 (7.8%) -1.000 CREB Signaling in Neurons Neurotransmitters and other nervous system signaling; cellular growth and proliferation and development 8.20 E -03 11/185 (5.9%) -1.000 Agrin Interactions at Neuromuscular Junction Neurotransmitters and other nervous system signaling 3.16 E -02 5/69 (7.2%) -1.000 All canonical pathways with a z-score of ≤-1.000 or ≥+1.000 are listed. Pathways with a significant z-score of ≤-2.000 or ≥+2.000 are depicted in bold. Genes ratio=the number and percentage of genes differentially expressed in ratio to the total number of genes involved in the pathway. A partial opposite response due to irinotecan administration presented itself via the upregulation of RhoGDI and PTEN signaling, indicative of growth suppression (Table 1A). The AHR pathway and the p70S6K signaling pathways were not regulated in the AL groups. Tumor transcriptome analysis Principal component analysis Next, the transcriptomes of the tumor samples were analyzed using a similar approach as for the liver samples. With a total of 59.49% of the variance explained by PC1 and 10.88% by PC2, the PCA plot of the tumor samples of the four experimental groups showed high heterogeneity among the groups with large intragroup variability (Figure 3A).The individual groups were not clearly separated as clusters, and showed only minor differences between groups. The tumor tissue of the fasting vehicle group showed the smallest intragroup