TSPAN8 and hepatocellular carcinoma: TIMP1 activates PI3K/Akt pathways via CD63 binding, preserving scPAS + cell stemness characteristics (Xu et al., 2025); TSPAN8 amplifies cellular basement membrane adhesion capacity by regulating integrin α6β4 membrane localization, providing anchorage sites for tumor cell vascular invasion; SPINK1 inhibits trypsin-like serine protease activity, mitigating tumor cell apoptosis from excessive protease activation, with its overexpression significantly correlating with increased vascular invasion and recurrence risk in HCC patients (Li et al., 2025).