The progression from early stage to middle stage LADC can be potentially induced by the hypoxic tumor microenvironment, the dysfunctions of NOTCH1 and ITGA4 (CD49d) signaling, the regulation of miR-30c-2 and miR-27b, the epigenetic modifications of VIM, MYH9, MDM4, and ETS1, and the dysregulation of cellular functions, such as angiogenesis, ECM remodeling, and EMT. Here, MDM4 is linked to neoplasm.