Osteopontin and latent-TGF β binding-protein 2 as potential diagnostic markers for HBV-related hepatocellular carcinoma.

Abstract

Chronic Hepatitis B (HB) is the main risk factor for chronic liver disease (CLD) and hepatocellular carcinoma (HCC) in many low-resource countries, where diagnosis is constrained by lack of clinical, histopathological and biomarker resources. We have used proteomics to detect plasma biomarkers that outperform α-Fetoprotein (AFP), the most widely used biomarker for HCC diagnosis in low-resource contexts. Deep-plasma proteome analysis was performed in HCC patients, patients with CLD and in HB-carrier controls from Thailand (South-East Asia) and The Gambia (West-Africa). Mass spectrometry profiling identified latent-transforming growth factor β binding-protein 2 (LTBP2) and Osteopontin (OPN) as being significantly elevated in HCC versus CLD and controls. These two proteins were further analyzed by ELISA in a total of 684 plasma samples, including 183 HCC, 274 CLD and 227 asymptomatic controls. When combined, LTBP2 and OPN showed an area under the receiver operating curve of 0.85 in distinguishing HCC from CLD in subjects with AFP <20 ng/mL. In a prospective cohort of 115 CLD patients from Korea, increased plasma levels of LTBP2 and/or OPN were detected in plasma collected over 2 years prior to diagnosis in 21 subjects who developed HCC. Thus, the combination of LTBP2 and OPN outperformed AFP for diagnosis and prediction of HCC and may therefore improve biomarker-based detection of HBV-related HCC.

• Authors: Andre Nogueira da Costa, Amelie Plymoth, Daniela Santos-Silva, Sandra Ortiz-Cuaran, Suzy Camey, Paule Guilloreau, Suleeporn Sangrajrang, Thiravud Khuhaprema, Maimuna Mendy, Olufunmilayo A Lesi, Hee-Kyung Chang, Jin-Kyoung Oh, Duk-Hee Lee, Hai-Rim Shin, Gregory D Kirk, Philippe Merle, Laura Beretta, Pierre Hainaut
• Journal: International journal of cancer (Int J Cancer) Vol. 136 Issue 1 Pg. 172-81 (Jan 01 2015) ISSN: 1097-0215 [Electronic] United States
• PMID: 24803312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 UICC.

Chemical References

• Biomarkers, Tumor
• LTBP2 protein, human
• Latent TGF-beta Binding Proteins
• Osteopontin

Topics

• Area Under Curve
• Biomarkers, Tumor (blood)
• Carcinoma, Hepatocellular (blood, diagnosis, virology)
• Case-Control Studies
• Early Detection of Cancer
• Hepatitis B, Chronic (blood)
• Humans
• Latent TGF-beta Binding Proteins (blood)
• Liver Neoplasms (blood, diagnosis, virology)
• Osteopontin (blood)
• Poverty
• ROC Curve