PIK3CA and hepatocellular carcinoma: Under the hypoxic environment, HIF-2 overexpression may drive NAFLD–HCC development by triggering the PI3K/Akt/mTOR cascade and inducing lipid reprogramming [192], while HIF-1α stabilization forces the switching from OXPHOS to aerobic glycolysis by upregulating glycolytic enzymes and LDH [193].