Fig. 5
Simulated VEGF/Sema ligand-receptor binding on endothelial cells. a VEGFR2 (left), VEGFR1 (middle), and Sema3-NRP1 (right) binding in benign prostate (n = 12), primary tumors (n = 49) and metastatic tumors (n = 27) in the GSE35988 dataset. The p-values are marked as follows: a single * indicates p < 0.05, a double ** indicates p < 0.01, and a triple *** indicates p < 0.001. b VEGF secretion and total Sema3 secretion most strongly affect their respective ligand-receptor complexes although weak competitive effects are observed. Lines represent least squares fits of the log-transformed simulated receptor binding data to the gene expression data. R2 values represent the proportion of variance explained by the least squares fit. c Scatter plots of simulated VEGFA-VEGFR2 and Sema3-NRP-PlxnA across tissue types show that only fraction of the metastatic samples fall into the expected anti-VEGFA responsive region, i.e. high VEGFA-VEGFR2 signaling and low Sema3-NRP-PlxnA signaling. Gradients correlate with expected favorability for angiogenesis: darker red for higher VEGFA-VEGFR2 and darker blue for lower Sema3-NRP-PlxnA. Colors indicate tissue type: Benign (green); Localized (orange); Metastasis (gray)