Recently, in vivo and in vitro studies have shown that twist-related protein 1 (Twist1), neurogenic locus notch homolog protein 4 (Notch4), hypoxia inducible factor (HIF)-1a, EPH receptor A2 (EphA2), matrix metalloproteinase (MMP)-1, 2, − 9, − 14, and vascular endothelial (VE)-cadherin are potential therapeutic targets and prognostic indicators in VM+ tumor samples [22, 56]. The gene discussed is NOTCH4; the disease is neoplasm.