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Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

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Duarte-Salles et al. - 2016 - Circulating Osteopontin and Prediction of Hepatoce.pdfAccepted version382.14 kBAdobe PDFView/Open
Title: Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population
Authors: Duarte-Salles, T
Misra, S
Stepien, M
Plymoth, A
Muller, DC
Overvad, K
Olsen, A
Tjonneland, A
Baglietto, L
Severi, G
Boutron-Ruault, MC
Turzanski-Fortner, R
Kaaks, R
Boeing, H
Aleksandrova, K
Trichopoulou, A
Lagiou, P
Bamia, C
Pala, V
Palli, D
Mattiello, A
Tumino, R
Naccarati, A
Bueno-de-Mesquita, HB
Peeters, PH
Weiderpass, E
Quiros, JR
Agudo, A
Sanchez-Cantalejo, E
Ardanaz, E
Gavrila, D
Dorronsoro, M
Werner, M
Hemmingsson, O
Ohlsson, B
Sjöberg, K
Wareham, NJ
Khaw, KT
Bradbury, KE
Gunter, MJ
Cross, AJ
Riboli, E
Jenab, M
Hainaut, P
Beretta, L
Item Type: Journal Article
Abstract: We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between pre-diagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested-case control study was conducted within the EPIC cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function and alpha-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95%CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable=1.30; 95%CI:1.14-1.48). The association was stronger among cases diagnosed within two years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC=0.86). For cases diagnosed within two years, the combination of OPN and AFP was best able to predict HCC risk (AUC=0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within two years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis.
Issue Date: 23-Jun-2016
Date of Acceptance: 15-Jun-2016
URI: http://hdl.handle.net/10044/1/34705
DOI: https://dx.doi.org/10.1158/1940-6207.CAPR-15-0434
ISSN: 1940-6215
Publisher: American Association for Cancer Research
Journal / Book Title: Cancer Prevention Research
Volume: 9
Copyright Statement: © 2016 American Association for Cancer Research. This is the accepted version of an article published in Cancer Prevention Research. The final version of record is available from: http://dx.doi.org/10.1158/1940-6207.CAPR-15-0434.
Sponsor/Funder: University Medical Center Utrecht
Imperial College Trust
Funder's Grant Number: N/A
P47328
Keywords: Oncology & Carcinogenesis
1103 Clinical Sciences
1112 Oncology And Carcinogenesis
Publication Status: Published
Article Number: 758
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care



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