Identification of osteopontin as a novel marker for early hepatocellular carcinoma - PubMed (original) (raw)

Identification of osteopontin as a novel marker for early hepatocellular carcinoma

Sufen Shang et al. Hepatology. 2012 Feb.

Abstract

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.

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Figures

Fig. 1

OPN identification by mass spectrometry in plasma from patients with cirrhosis or HCC. A) OPN was identified by mass spectrometry with 12 unique peptides leading to 40.4% sequence coverage. B) OPN abundance was higher in plasma of patients with HCC compared to plasma of patients with cirrhosis (P=0.03). OPN abundance is shown as the total number of tandem mass spectra assigned to that protein in each sample.

Fig. 2

Plasma levels of OPN among healthy individuals and those with chronic hepatitis C (CHC), cirrhosis and HCC from Cohort 1. The box refers to the 25th and 75th percentile values with a line indicating the median levels, whereas the interquartile range extends outside the box. Points outside the interquartile range are outliers. HCC had higher OPN plasma levels compared with cirrhosis, CHC and healthy control groups (p<0.0001).

Fig. 3

Receiver operating characteristics (ROC) curve evaluating those with HCC and cirrhosis controls in Cohort 1. The area under the ROC curve (AUC) is shown with its 95% confidence intervals. A) all cirrhosis vs all HCC patients; B) HCV-related cirrhosis vs HCV-related HCC; C) cirrhosis vs early stage HCC; D) cirrhosis vs HCC with AFP levels below 20 ng/ml. AFP is represented by the solid line, OPN by the dash line, and the combination of AFP and OPN by the dotted line.

Fig. 4

Evaluation of OPN and AFP performance in HCC patients and patients with cirrhosis or CHB, enrolled in Cohort 2. A) Plasma levels of OPN in healthy controls, patients with cirrhosis or chronic HBV (CHB) and HCC patients. The box refers to the 25th and 75th percentile values with a line indicating the median levels, whereas the interquartile range extends outside the box. Points outside the interquartile range are outliers. B) The area under the ROC curve (AUC) is shown together with the 95% confidence intervals for all cirrhosis and CHB vs HCC patients, C) for HBV-related cirrhosis and CHB vs HBV-related HCC, D) for all cirrhosis and CHB vs HCC patients with AFP levels below 20 ng/ml. Solid line: AFP, dash line: OPN and dotted line: combination of AFP and OPN.

Fig. 5

Plasma levels of OPN in pre-diagnosis samples. OPN was measured in plasma collected from 22 patients A) at time of diagnosis; B) 6-12 months prior to diagnosis; C) 12-24 months prior to diagnosis and D) more than 24 months before diagnosis. The graphs also show the levels of AFP in the same samples. The dotted lines represent the cutoffs for AFP (20 ng/ml) and for OPN (91 ng/ml).

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Identification of osteopontin as a novel marker for early hepatocellular carcinoma - PubMed (original) (raw)