Tumor microenvironment‐dependent epigenetic imprinting in the vasculature predicts colon cancer outcome

Abbreviations 5-Aza 5-Aza-2’-deoxycytidine CCDC80 coiled-coil domain containing 80 COL12A1 collagen type XII alpha 1 chain CRC colorectal cancer DDR2 discoidin domain receptor tyrosine kinase 2 DEGs differenital expressed genes DFS disease-free survival DNA desoxyribonucleic acid ECs endothelial cells GBP guanylate binding protein HLA-DRA/-DPB1/-DQB1/-DQA1 major histocompatibility complex, class II-DR alpha/DP beta 1/DQ beta 1/DQ alpha 1 IFN interferon LIFR leukemia inhibitory factor receptor LRMP lymphoid restricted membrane protein NECs normal endothelial cells MERTK MER proto-oncogene, tyrosine kinase Pat patient PBMCs peripheral blood mononuclear cells PDGFRB platelet derived growth factor receptor beta SNX10 sorting nexin 10 STC2 stanniocalcin 2 SPARCL1 secreted protein acidic and cysteine rich like 1 TECs tumor endothelial cells TGFB2 transforming growth factor beta 2 Th T helper TME tumor microenvironment VE-cadherin vascular endothelial-cadherin Dear Editor, Tumor microenvironment (TME)-dependent stromal cell plasticity governs tumor development and therapy response. (E) Integrated analysis (gene overlap percentage) of the transcriptome, methylome and genome reveals an increased methylome/transcriptome overlap as compared to the genome/transcriptome (left). The relationship of the Th1-associated DEGs in cultivated TECs with the immuno-angiostatic Th1-TME was supported by functional enrichment analysis identifying downregulated terms, including “positive regulation of cell migration/motility” and “angiogenesis” (Figure 1B). Analyses of an inverse relation of methylation and gene expression identified the genes LIFR, LRMP/JAW1, MERTK, and SNX10 with increased transcription and reduced methylation, as well as CCDC80, COL12A1, DDR2, PDGFRB, STC2 and TGFB2 in the opposite direction in Th1-TEC DEGs (Figure 1E, Supplementary Table S6).