Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population.
Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population.
复制标题
DOI：
10.1158/1940-6207.capr-15-0434
复制
发表时间：
2016-09
期刊：
影响因子：
--
通讯作者：
Beretta L
中科院分区：
文献类型：
--
作者：
Duarte-Salles T;Misra S;Stepien M;Plymoth A;Muller D;Overvad K;Olsen A;Tjønneland 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;Quirós JR;Agudo A;Sánchez-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
我们之前发现骨桥蛋白 (OPN) 是一种有前途的早期检测肝细胞癌 (HCC) 的标记物。在这项研究中，我们在一个大型人群队列中调查了诊断前循环 OPN 水平与 HCC 发病率之间的关联。在 EPIC 队列中进行了一项巢式病例对照研究。在平均 4.8 年的随访期间，发现了 100 例 HCC 病例。每个病例与两个对照相匹配，并测量基线血浆样本中的 OPN 水平。还进行了病毒性肝炎、肝功能和甲胎蛋白（AFP）检测。使用条件逻辑回归模型计算 OPN 水平与 HCC 相关的多变量比值比 (OR) 和 95% 置信区间 (95%CI)。构建受试者工作特征曲线以确定 OPN 单独使用或与其他肝脏生物标志物联合使用在 HCC 预测中的辨别准确性。 OPN 水平与 HCC 风险呈正相关（每增加 10%，OR 多变量=1.30；95%CI：1.14–1.48）。在随访两年内诊断出的病例中，这种关联性更强。在 OPN 中添加肝功能测试可改善对发展为 HCC 的受试者的辨别能力 (AUC=0.86)。对于两年内诊断的病例，OPN 和 AFP 的组合最能预测 HCC 风险（AUC=0.88）。该低风险人群中 HCC 的最佳预测模型是 OPN 与肝功能测试相结合。在诊断后两年内，OPN 和 AFP 的组合可以最好地预测 HCC 的发展，这表明测量 OPN 和 AFP 可以独立于肝病诊断来识别高危人群。
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.