Proteome Multimarker Panel for the Early Detection of Hepatocellular Carcinoma: Multicenter Derivation, Validation, and Comparison.

Conventional methods for the surveillance of hepatocellular carcinoma (HCC) by imaging, with and without serum tumor markers, are suboptimal with regard to accuracy. We aimed to develop and validate a reliable serum biomarker panel for the early detection of HCC using a proteomic technique. This multicenter case-control study comprised 727 patients with HCC and patients with risk factors but no HCC. We developed a multiple reaction monitoring-mass spectrometry (MRM-MS) multimarker panel using 17 proteins from the sera of 398 patients. Area under the receiver operating characteristics curve (AUROC) values of this MRM-MS panel with and without α-fetoprotein (AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II) were compared. The combination and standalone MRM-MS panels had higher AUROC values than AFP in the training (0.940 and 0.929 vs 0.775, both < 0.05), test (0.894 and 0.893 vs 0.593, both < 0.05), and confirmation sets (0.961 and 0.937 vs 0.806, both < 0.05) in detecting small single HCC. The combination and standalone MRM-MS panels had significantly higher AUROC values than the GALAD score (0.945 and 0.931 vs 0.829, both < 0.05). Our proteome 17-protein multimarker panel distinguished HCC patients from high-risk controls and had high accuracy in the early detection of HCC.