Multiple molecular mechanisms expressed by these genetic (e.g., epidermal growth factor receptor (EGFF) overexpression, CDKN2A-p16 deletion, IDH1/2, and PTEN mutations) and epigenetic factors (e.g., non-coding RNA regulation, DNA methylation, histone modification, and chromatin remodeling) support very active crosstalk between the constituents of the TME, resulting in uncontrolled tumor proliferation, angiogenesis, and invasion [3,5]. Here, CDKN2A is linked to neoplasm.