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

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.

Serum osteopontin is a predictor of prognosis for HBV‑associated acute‑on‑chronic liver failure

“…OPN is involved in cell migration and inflammatory signaling, and previous studies have demonstrated that OPN was associated with hepatic inflammation and invasiveness in hepatocellular carcinoma (HCC) (8,9,21). In line with these experimental observations, an association of circulating OPN levels and HCC incidence has previously been demonstrated in a population cohort of more than 520,000 subjects from ten Western European countries (21).…”

“…In line with these experimental observations, an association of circulating OPN levels and HCC incidence has previously been demonstrated in a population cohort of more than 520,000 subjects from ten Western European countries (21). As cell proliferation is among the key mechanisms in HCC and liver repair (8,(22)(23)(24), high levels of OPN may suggest tumor progression or liver regeneration.…”

Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases

“…These include the following markers: epithelial cell adhesion molecule, osteopontin, surface marker vimentin, transforming growth factor beta/sirtuin, and DNA repair pathway members. These novel biomarkers reflect biological significance in HCC …”

Should AFP (or Any Biomarkers) Be Used for HCC Surveillance?

“…Other emerging biomarkers include osteopontin (OPN) [81–83], latent TGF-beta binding protein I (LTBP1) [84], latent TGF-beta binding protein II (LTBP2) [83], DKK1 [85], midkine (MDK) [86, 87], GP73 [88, 89], glypican 3 (GPC3) [90], and a variety of miRNAs [91, 92]. These markers are under active investigation and none of them have been approved for clinical use.…”