乳腺肿瘤高度血管化，并对血管生成在生长、进展和转移中依赖。与其他实体肿瘤一样，乳腺肿瘤的血管系统也显示出漏血和扭曲的特征，从而抑制免疫细胞浸润，并对抗癌药物和放疗的疗效降低。肿瘤和基质细胞中的表观遗传重编程包括DNA甲基化的显著改变，导致促血管生成因子和抗血管生成因子的表达失衡，进而引起血管生成障碍。因此，了解DNA甲基化对乳腺肿瘤血管生成的调控可能为设计治疗靶点开辟新途径。我们的综述手稿总结了DNA甲基化在调控血管生成中的影响的现代知识。此外，我们还确定了在乳腺肿瘤中与DNMT同工酶共调控且富含CpG岛的内皮细胞特异的一批新的促血管生成基因。我们的分析显示，促血管生成基因的启动子在肿瘤中是低甲基化的，而抗血管生成基因是高甲基化的，并且这种甲基化状态反映在它们的表达模式上。有趣的是，这批新的促血管生成基因的启动子DNA甲基化强度与患者的生存结果显著相关。版权所有 © 2023 Elsevier Inc. 发表

Breast tumors are highly vascularized and dependent on angiogenesis for growth, progression and metastasis. Like other solid tumors, vasculature in breast tumors also display leaky and tortuous phenotype and hence inhibit immune cell infiltration, show reduced efficacy to anticancer drugs and radiotherapy. Epigenetic reprogramming including significant alterations in DNA methylation in tumor and stromal cells generate an imbalance in expression of pro- and anti-angiogenic factors and subsequently lead to disordered angiogenesis. Hence, understanding DNA methylation-based regulation of angiogenesis in breast tumors may open new avenues for designing therapeutic targets. Our present review manuscript summarized contemporary knowledge of influence of DNA methylation in regulating angiogenesis. Further, we identified novel set of pro-angiogenic genes enriched in endothelial cells which are coregulated with DNMT isoforms in breast tumors and harboring CpG islands. Our analysis revealed promoters of pro-angiogenic genes were hypomethylated and anti-angiogenic genes were hypermethylated in tumors and further reflected on their expression patterns. Interestingly, promoter DNA methylation intensities of novel set of pro-angiogenic genes significantly correlated to patient survival outcome.Copyright © 2023. Published by Elsevier Inc.