title: 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.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Andre Nogueira
authors.initials: AN
authors.lastname: da Costa
authors.forename: Amelie
authors.initials: A
authors.lastname: Plymoth
authors.forename: Daniela
authors.initials: D
authors.lastname: Santos-Silva
authors.forename: Sandra
authors.initials: S
authors.lastname: Ortiz-Cuaran
authors.forename: Suzy
authors.initials: S
authors.lastname: Camey
authors.forename: Paule
authors.initials: P
authors.lastname: Guilloreau
authors.forename: Suleeporn
authors.initials: S
authors.lastname: Sangrajrang
authors.forename: Thiravud
authors.initials: T
authors.lastname: Khuhaprema
authors.forename: Maimuna
authors.initials: M
authors.lastname: Mendy
authors.forename: Olufunmilayo A
authors.initials: OA
authors.lastname: Lesi
authors.forename: Hee-Kyung
authors.initials: HK
authors.lastname: Chang
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Oh
authors.forename: Duk-Hee
authors.initials: DH
authors.lastname: Lee
authors.forename: Hai-Rim
authors.initials: HR
authors.lastname: Shin
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Kirk
authors.forename: Philippe
authors.initials: P
authors.lastname: Merle
authors.forename: Laura
authors.initials: L
authors.lastname: Beretta
authors.forename: Pierre
authors.initials: P
authors.lastname: Hainaut
mesh_terms: D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D016022:Case-Control Studies; D055088:Early Detection of Cancer; D019694:Hepatitis B, Chronic / Q000097:blood*; D006801:Humans; D053779:Latent TGF-beta Binding Proteins / Q000097:blood*; D008113:Liver Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000821:virology; D053495:Osteopontin / Q000097:blood*; D011203:Poverty; D012372:ROC Curve
chemical_list: D014408:Biomarkers, Tumor; C509035:LTBP2 protein, human; D053779:Latent TGF-beta Binding Proteins; D053495:Osteopontin
keywords: LTBP2; biomarkers; chronic liver disease; hepatocellular carcinoma; osteopontin