Osteopontin (OPN), a secreted extracellular matrix protein, that interacts with Integrins, functions as a Th1 cytokine, is involved in tissue remodeling (Lund et al. 2009) and intricately linked to the JAK2/STAT3 and PI3K/Akt signaling pathways in HCC, contributing to tumor growth, invasion, and metastasis (Desert et al. 2022; Wu et al. 2022; Yu et al. 2018). This evidence concerns the gene SPP1 and hepatocellular carcinoma.