SPINT2 and hepatocellular carcinoma: More generally, changes in DNA methylation gradually increase from cirrhosis, dysplastic nodules and HCC, and aberrant methylation of four gatekeeper genes (testis-specific Y-encoded-like protein 5 (TSPYL5); Potassium Voltage-Gated Channel Subfamily A Member 3 (KCNA3); lactate dehydrogenase B (LDHB); and serine peptidase inhibitor Kunitz Type 2 (SPINT2)) have recently been linked to the transition to early HCC [39,47].