背景：本次研究的目的在于去发现一种新的生物标志物，它能提高甲胎蛋白对肝硬化病人中肝癌的监视功能。方法：我们通过对肝硬化或肝癌病人进行血浆蛋白组学分析，证实来自两个不同地域队列中的肝癌生物学标记涵盖了不同病因学的肝癌。结果：通过对18例肝硬化和17例肝癌病人的高分离血浆进行质谱分析，发现肝癌组的骨桥蛋白相比肝硬化组明显升高。随后将312人的血浆分于两个独立队列中进行检测，其中包括131例肝癌病人，76例肝硬化病人，52例慢性乙肝和丙肝病人，和53例健康对照。相比肝硬化、CHC、CHB或健康对照组，肝癌病人血浆中骨桥蛋白在两个队列中明显升高。在肝硬化和肝癌的对照中，与AFP相比，OPN或OPN与AFP联合有更好的受试者工作特性曲线下面积。在对比肝硬化和以下肝癌组中，其中包括：丙肝相关型肝癌、乙肝相关型肝癌以及早期肝癌，OPN的整体表现要明显好于AFP。 OPN在AFP阴性的肝癌患者中也有很好的敏感性。在一项初步的前瞻性研究中，其中包括22例患者在随访期发展为肝癌，骨桥蛋白在确诊肝癌一年前就已经升高了。结论：结论：在所有的肝癌研究组中，骨桥蛋白要比甲胎蛋白的敏感性更高。此外，在从确诊肝癌1年前获得的血清中发现，骨桥蛋白仍可被完好检测。BACKGROUND AND AIMS: The aim of this study was to identify a biomarker that could improve alpha-fetoprotein(AFP) performance in hepatocellular carcinoma (HCC) surveillance among patients with cirrhosis.
METHODS: We performed proteomic profiling of plasma from patients with cirrhosis or HCC and validated selected candidate HCC biomarkers in two geographically distinct cohorts to include HCC of different etiologies.
RESULTS: Mass spectrometry profiling of highly fractionated plasma from 18 cirrhosis and 17 HCC patients identified osteopontin (OPN) as significantly up-regulated in HCC cases, compared to cirrhosis controls. OPN levels were subsequently measured in 312 plasma samples collected from 131 HCC patients, 76 cirhosis patients, 52 chronic hepatitis C (CHC) and B (CHB) patients, and 53 healthy controls in two independent cohorts. OPN plasma levels were significantly elevated in HCC patients, compared to cirrhosis, CHC, CHB, or healthy controls, in both cohorts. OPN alone or in combination with AFP had significantly better area under the receiver operating characteristic curve, compared to AFP, in comparing cirrhosis and HCC in both cohorts. OPN overall performance remained higher than AFP in comparing cirrhosis and the following HCC groups: HCV-related HCC, HBV-associated HCC, and early HCC.OPN also had a good sensitivity in AFP-negative HCC. In a pilot prospective study including 22 patients who developed HCC during follow-up, OPN was already elevated 1 year before diagnosis.
CONCLUSIONS: OPN was more sensitive than AFP for the diagnosis of HCC in all studied HCC groups. In addition, OPN performance remained intact in samples collected 1 year before diagnosis .
吉林大学第一医院肝胆胰内科 杨太忠 摘译
本文首次发表于[Hepatology. 2012;55(2):483-490.]
Identification of Osteopontin as a Novel Marker for Early Hepatocellular Carcinoma
Abstract
