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

Talita Duarte-Salles, Sandeep Misra, Magdalena Stepien, Amelie Plymoth, David Muller, Kim Overvad, Anja Olsen, Anne Tjønneland, Laura Baglietto, Gianluca Severi, Marie Christine Boutron-Ruault, Renee Turzanski-Fortner, Rudolf Kaaks, Heiner Boeing, Krasimira Aleksandrova, Antonia Trichopoulou, Pagona Lagiou, Christina Bamia, Valeria Pala, Domenico PalliAmalia Mattiello, Rosario Tumino, Alessio Naccarati, H. B. Bueno-De-Mesquita, Petra H. Peeters, Elisabete Weiderpass, J. Ramôon Quiros, Antonio Agudo, Emilio Sanchez-Cantalejo, Eva Ardanaz, Diana Gavrila, Miren Dorronsoro, Mårten Werner, Oskar Hemmingsson, Bodil Ohlsson, Klas Sjöberg, Nicholas J. Wareham, Kay Tee Khaw, Kathryn E. Bradbury, Marc J. Gunter, Amanda J. Cross, Elio Riboli, Mazda Jenab, Pierre Hainaut, Laura Beretta

Research output: Contribution to journalArticlepeer-review


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 prediagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (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 a-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 2 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 2 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 2 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.

Original languageEnglish
Pages (from-to)758-765
Number of pages8
JournalCancer Prevention Research
Issue number9
Publication statusPublished - Sep 1 2016

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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