A Novel Biomarker Panel for the Early Detection and Risk Assessment of Hepatocellular Carcinoma in Patients with Cirrhosis

Abstract

Novel biomarkers for HCC surveillance in cirrhotic patients are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. The present study is to further validate the performance of OPN and identify fatty acids (FAs) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 cirrhotic patients under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and pre-diagnostic serum levels of AFP, OPN and 46 FAs. OPN performance was higher than AFP in detecting pre-diagnosis HCCs and the combination with AFP further improved OPN's performance. For patients with a diagnosis of HCC within 18 months of follow-up (HCC<18m), AUC for OPN+AFP was 0.77. Abundance of 11 FAs (four long-chain saturated FAs (SFAs), four n-3 poly-unsaturated FAs (PUFAs) and three n-6 PUFAs) were statistically different between patients who developed HCC and those who didn't. Abundance changes correlated with time to diagnosis for the PUFAs but not for the SFAs. Adding arachidic acid (20:0) and n-3 docosapentaenoic acid (22:5n3) to OPN and AFP improved the discriminatory performance (AUC=0.83). AUC for this panel reached 0.87 for HCC<18m (82% sensitivity at 81% specificity). In conclusion, we identified a panel of 4 markers with strong performances that could have significant utility in HCC early detection in patients with cirrhosis under surveillance.