Furthermore, P4 panel performed significantly better than PIVKA-II in AFP-negative HCC (Validation Set: HCC/LC: AUC: 0.963 vs. 0.893, sensitivity: 0.857 vs. 0.833; HCC/HC: AUC: 0.984 vs. 0.938, sensitivity: 0.952 vs. 0.833) (Fig. 6B, Supplementary Fig. 5c, d), as well as significantly better than AFP in PIVKA-II negative HCC (Validation Set: HCC/LC: AUC: 0.946 vs. 0.868, sensitivity: 0.813 vs. 0.563; HCC/HC: AUC: 0.958 vs. 0.902, sensitivity: 0.875 vs. 0.563) (Fig. 6c, Supplementary Fig. 5e, f). Here, AFP is linked to hepatocellular carcinoma.