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

Authors

Ilvira M Khan
Donjeta Gjuka
Jingjing Jiao
Xiaoling Song
Ying Wang
Jing Wang
Peng Wei
Hashem B El-Serag
Jorge A Marrero
Laura Beretta

Publication Date

6-1-2021

Journal

Cancer Prevention Research

DOI

10.1158/1940-6207.CAPR-20-0600

PMID

33685927

PMCID

PMC8225562

PubMedCentral® Posted Date

12-1-2021

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Adult, Aged, Biomarkers, Tumor, Carcinoma, Hepatocellular, Case-Control Studies, Early Detection of Cancer, Feasibility Studies, Follow-Up Studies, Humans, Incidence, Liver Cirrhosis, Liver Neoplasms, Male, Middle Aged, ROC Curve, Risk Assessment, Watchful Waiting

Abstract

Novel biomarkers for hepatocellular carcinoma (HCC) surveillance in patients with cirrhosis are urgently needed. We previously identified osteopontin (OPN) as a promising biomarker for the early detection of HCC. This study is to further validate the performance of OPN and identify fatty acids (FA) that could improve OPN's performance in HCC risk assessment in patients with cirrhosis. To that end, we selected 103 patients with cirrhosis under surveillance. Among them, 40 patients developed HCC during follow-up. We investigated in these 103 patients, the association between HCC incidence and prediagnostic serum levels of AFP, OPN, and 46 FAs. OPN performance was higher than AFP in detecting prediagnosis 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 < 18 months), AUC for OPN + AFP was 0.77. Abundance of 11 FAs [four long-chain saturated FAs (SFA), four n-3 poly-unsaturated FAs (PUFA), and three n-6 PUFAs] were statistically different between patients who developed HCC and those who did not. 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 < 18 months (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. PREVENTION RELEVANCE: This study identified a panel of 4 biomarkers that identifies with high performance patients with cirrhosis at high risk for HCC. This panel could have utility in HCC early detection in patients with cirrhosis under surveillance.

Comments

Associated Data