As shown in Figure 6C, our results reveal that the hypoxic tumor microenvironment and the genetic and epigenetic dysregulation could lead to the alteration of NOTCH1 and ITGA4 signaling pathways, resulting in abnormal angiogenesis, EMT, apoptosis, ECM remodeling, and cell migration to cause early stage LADC to progress to middle stage LADC. Here, NOTCH1 is linked to neoplasm.