A proteomics approach exploited to analyze the secretory releasing proteome of HBV-associated HCC has showed that among 1365 proteins identified in serum-free conditioned media, levels of AFP, OPN, pregnancy-specific beta-1-glycoprotein-9 (PSG-9) and matrix metalloproteinase-1 (MMP-1), members of transforming growth factor-β (TGF-β)-signaling pathway were the most significantly increased in HCC patients [128]. The gene discussed is SPP1; the disease is hepatocellular carcinoma.