Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Cancer Research Center, Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
Department of Clinical Laboratory, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
Sci Rep. 2017 Jan 12;7:38918. doi: 10.1038/srep38918.
The accuracy of current biomarkers for the diagnosis of hepatocellular carcinoma (HCC), especially chronic Hepatitis B Virus (HBV)-related HCC, is limited. Recent progress in glycoproteomics has provided a novel platform for screening novel serological biomarkers of HCC. In this study, lectin affinity chromatography by Maackia amurensis lectin (MAL) and iTRAQ combined with mass spectrometric analysis were performed to enrich and identify the glycoprotein fractions in serum samples from HBV-related HCC patients and from healthy controls. Seventeen differential MAL-associated glycoproteins were identified. Among them, Galectin 3 binding protein (Gal-3BP) was selected for further evaluated by ELISA analysis and showed a high diagnostic potential of HBV-related HCC, with the AUC of 0.898 and a sensitivity, specificity and accuracy of 80.00%, 93.75% and 86.88%, respectively. Moreover, we constructed a predictive model through the combined use of serum Gal-3BP and Alpha Fetoprotein (AFP), which improved the sensitivity (from 87.5% to 95%), specificity (from 93.75% to 95%) and accuracy (from 90.63% to 95%) of diagnosing early HCC. These data suggested serum Gal-3BP level is a promising biomarker to identify HBV-related HCC and the combined use of serum Gal-3BP and AFP improves the diagnostic potential of HBV-HCC compared with AFP alone in current clinical practice.
目前用于诊断肝细胞癌(HCC),特别是慢性乙型肝炎病毒(HBV)相关 HCC 的生物标志物的准确性有限。糖蛋白质组学的最新进展为筛选 HCC 的新型血清生物标志物提供了新的平台。在这项研究中,采用槐凝集素(MAL)亲和层析和 iTRAQ 联合质谱分析,对 HBV 相关 HCC 患者和健康对照者血清样本中的糖蛋白进行了富集和鉴定。鉴定出 17 种差异 MAL 相关糖蛋白。其中,半乳糖凝集素 3 结合蛋白(Gal-3BP)通过 ELISA 分析进行了进一步评估,显示出对 HBV 相关 HCC 的高诊断潜力,AUC 为 0.898,灵敏度、特异性和准确性分别为 80.00%、93.75%和 86.88%。此外,我们通过联合使用血清 Gal-3BP 和甲胎蛋白(AFP)构建了一个预测模型,提高了早期 HCC 的诊断灵敏度(从 87.5%提高到 95%)、特异性(从 93.75%提高到 95%)和准确性(从 90.63%提高到 95%)。这些数据表明,血清 Gal-3BP 水平是一种很有前途的生物标志物,可用于识别 HBV 相关 HCC,与单独使用 AFP 相比,联合使用血清 Gal-3BP 和 AFP 可提高 HBV-HCC 的诊断潜力,适用于当前的临床实践。