Furthermore, mIHC analysis confirmed that AREG and EGFR/ERBB2, as well as NAMPT and ITGA5/ITGB1, were overexpressed in the PMC_P region (Fig. 5e, f), verified in clinical specimen (Supplementary Fig. 3c and Tables 9, 10) suggesting that these LRPs play a critical role in mediating tumor initiation in the tipping point. This evidence concerns the gene AREG and neoplasm.