The aim of this study was to identify a
biomarker that could improve
alpha-fetoprotein (AFP) performance in
hepatocellular carcinoma (HCC) surveillance among patients with
cirrhosis. We performed proteomic profiling of plasma from patients with
cirrhosis or HCC and validated selected candidate HCC
biomarkers in two geographically distinct cohorts to include HCC of different etiologies. Mass spectrometry profiling of highly fractionated plasma from 18
cirrhosis and 17 HCC patients identified
osteopontin (OPN) as significantly up-regulated in HCC cases, compared to
cirrhosis controls. OPN levels were subsequently measured in 312 plasma samples collected from 131 HCC patients, 76
cirrhosis patients, 52
chronic hepatitis C (CHC) and B (CHB) patients, and 53 healthy controls in two independent cohorts. OPN plasma levels were significantly elevated in HCC patients, compared to
cirrhosis, CHC, CHB, or healthy controls, in both cohorts. OPN alone or in combination with AFP had significantly better area under the receiver operating characteristic curve, compared to AFP, in comparing
cirrhosis and HCC in both cohorts. OPN overall performance remained higher than AFP in comparing
cirrhosis and the following HCC groups: HCV-related HCC, HBV-associated HCC, and early HCC. OPN also had a good sensitivity in AFP-negative HCC. In a pilot prospective study including 22 patients who developed HCC during follow-up, OPN was already elevated 1 year before diagnosis.
CONCLUSION: OPN was more sensitive than AFP for the diagnosis of HCC in all studied HCC groups. In addition, OPN performance remained intact in samples collected 1 year before diagnosis.