Fig. 4

Major signaling pathways enriched by up-regulated genes in FSTL1-knockdown ccRCC cells by microarray assay. a Heat map of 105 differentially expressed genes (48 down-regulated and 57 up-regulated). b Reproducibility of the 105 differentially expressed genes in NRCC-shFSTL1-1 and NRCC-shFSTL1-2 cells (Pearson correlation coefficient r = 0.92; scope of linear model k = 0.86, P < 0.001). c Ranked by normalized enrichment score (NES), the top 11 gene sets (blue squares) enriched by up-regulated genes in response to FSTL1 knockdown are selected to plot the network. Intersection genes (green dots) with fold change > 2 were plotted to connect the gene sets. The gene sets fell into nuclear factor-кB (NF-κB)- and hypoxia-inducible factor (HIF)-related signaling subnetworks, respectively, which is connected by a histone deacetylase 1 (HDAC1)-related gene sets. d Enrichment plot of the representative gene set with the highest NES score in the NF-κB-related signaling subnetwork. e Enrichment plot of the representative gene set with the highest NES score in the HIF-related signaling subnetwork. The vertical dashed line in each plot denoted the point at which NES reached its maximum