Identification of Osteopontin as a Novel Marker for Early Hepatocellular Carcinoma

Abstract

This study was to identify a biomarker that could improve α-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 in order 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 upregulated 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 had also 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 a year prior to 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 a year prior to diagnosis.

Secretory/releasing proteome-based identification of plasma biomarkers in HBV-associated hepatocellular carcinoma

“…In this study, OPN was demonstrated to be a potential biomarker for the detection of HCC. This finding is consistent with a previous report suggesting OPN was more sensitive than AFP as a biomarker, and was a marker of early-stage HCC [26]. In addition, up-regulated OPN has been shown to indicate a poor prognosis for HCC [27].…”

Performance of diagnostic biomarkers in predicting liver fibrosis among hepatitis C virus-infected Egyptian children

“…The same authors found that OPN levels are a potential diagnostic marker for HCC, especially among high-risk groups of patients. Shang et al (2012) monitored serum OPN levels for one year before the diagnosis of HCVrelated HCC patients. Libra et al (2005) postulated that OPN might play a role in lymphomagenesis, particularly in the context of HCV infection.…”

Plasma Osteopontin as a Novel Diagnostic Biomarker for Early Detection of Hepatocellular Carcinoma.

“…This was supported by previous studies, who suggested the use of OPN as a diagnostic biomarker for HCC [25,26]. Shang et al added that OPN was markedly elevated in the plasma of HCC patients, and had been identified as a diagnostic biomarker, which could also improve AFP performance in HCC surveillance among patients with HBV or HCV related cirrhosis [27].…”

“…Shang et al reported that OPN has a good sensitivity in AFP negative HCC, indicating OPN as a better marker in the early stage of HCC, so the role of OPN and AFP in HCC diagnosis is complementary [27].…”