KEGG analysis of differentially co-upregulated genes in transcriptomic data of SPEN-deficient TECs and SPENi-transfected HUVECs revealed that the p53 signaling pathway was enriched in the top 20 markedly changed entries, consistent with that p53 signaling is critical for Spen ablation–induced tumor vessel normalization (Supplemental Figure 8, A–C). This evidence concerns the gene SPEN and neoplasm.