In blood, combining DMMs (such as HOXA1 and TSPYL5) with protein biomarkers (AFP, AFP-L3) or demographic factors exhibited 71–82% sensitivity for the early-stage HCC detection in two large clinical cohorts, which was superior over AFP and the combination of AFP, AFP-L3, and DCP [16,17]. Here, TSPYL5 is linked to hepatocellular carcinoma.