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 chronic liver disease (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 analysed 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 (ROC) of 0.85 in distinguishing HCC from CLD in subjects with α-Fetoprotein (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.

Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients

“…Individuals from the reference group presented no clinical evidence of liver disease. All study participants provided informed consent, and both Thailand and international institutional review boards approved the study protocol (21,34).…”

“…Several parameters were measured in the framework of the International Liver Cancer Study (ILCS) initiative in Thailand, including alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT), which are classical tests for liver function and latent-transforming growth factor β binding-protein 2 (LTBP2), a new candidate biomarker of HCC (21). In general, tests for liver function fail to discriminate HCC patients from controls [analysis of variance (ANOVA); ALP, P = 0.456, AST, P = 0.172, ALT, P* = 0.010], while LTBP2 values do (ANOVA; P*** < 10…”

The OPN Gene Polymorphism Confers the Susceptibility and Response to Ara-C Based Chemotherapy in Chinese AML Patients

“…The association between OPN and solid cancers has been reported in hepatocellular carcinoma, pancreatic Cancer and lung cancer [20,21,22]. Increased serum OPN concentrations occur in chronic myeloid leukemia, multiple myeloma, and acute myeloid leukemia [23].…”

Significant biomarkers for the management of hepatocellular carcinoma

“…High-sensitivity enzymelinked immuno sorbent assay (ELISA) and high-throughput detection methods are being used to find biomarkers [53]. Moreover, understanding the molecular pathogenesis of HCC could contribute to revealing cytokines and proteins that may represent useful biomarkers for HCC.…”