Another promising biomarker includes osteopontin (OPN), an acidic chemokine-like secreted phosphoglycoprotein found in ECM that functions via integrin-αv3/NF-κB/HIF-α, PI3K/Akt/NF-κB, and CD44-mediated signaling and can be used for early diagnosis of HCC [163,164]. This evidence concerns the gene SPP1 and hepatocellular carcinoma.