Hypoxia and necrosis determined as significant radiomic features played a central role in RCC progression by modulating critical signaling pathways including PI3K/AKT signaling, Notch signaling, Wnt signaling, and focal adhesion, governing stem-cell-like phenotype, cancer cell plasticity, metabolic reprogramming, epithelial-to-mesenchymal transition (EMT) closely associated with higher probability to escape the primary tumor and survive in an avascular metastatic site [2,5,21,38,39,40]. This evidence concerns the gene AKT1 and renal cell carcinoma.