Liver cancer Institute, Zhongshan Hospital, Shanghai, 200032, People's Republic of China.
J Cancer Res Clin Oncol. 2010 Aug;136(8):1151-9. doi: 10.1007/s00432-010-0762-6. Epub 2010 Feb 4.
The prognosis of HCC remains poor mainly because of the lack of diagnosis biomarkers especially in patients with cirrhosis background.
To identify serum biomarkers for HCC, we use cleavable stable isotope labeling (cICAT) combined with LC-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) to compare the serum proteome between liver cirrhosis and HCC patients. Sera from nine liver cirrhosis patients and nine HCC patients were selected for screening study. Then the alpha-1-acid glycoprotein (AGP) was chosen for validation by western blot. AGP was measured in the separate validation study including 52 HCC patients and 40 liver cirrhosis patients by rate nephelometry. Its value for HCC diagnosis from liver cirrhosis was also appreciated through receiver operating curve (ROC).
We quantified and identified 31 different proteins which include AGP, complement C4, haptoglobin, alpha-1-antitrypsin precursor, alpha-2-macroglobulin precursor, prothrombin precursor and ubiquitin carboxyl-terminal hydrolase 44 (USP44), etc. The serum concentration of AGP in HCC patients (n = 52) was significantly higher than in liver cirrhosis (n = 40) (P < 0.005) in validation study. AGP was useful for discrimination of the HCC cases from LC patients when the AFP levels were below 500 ng/ml. The area under curve (AUC) of the AGP and the combination of AGP and AFP were 0.834 (P < 0.0005, 95% CI: 0.734-0.934) and 0.880 (P < 0.0005, 95% CI, 0.789-0.970) separately, which are higher than AFP alone (0.538, P = 0.604, 95% CI: 0.386-0.689).
cICAT combined with LC-MS/MS-based serum proteome analysis can be useful in the screening of serum biomarkers for HCC. Alpha-1-acid glycoprotein combining AFP could aid the diagnosis of HCC.
肝癌的预后仍然很差，主要是因为缺乏诊断生物标志物，尤其是在肝硬化背景下。
为了鉴定肝癌的血清生物标志物，我们使用可裂解稳定同位素标记（cICAT）结合 LC-电喷雾电离串联质谱（LC-ESI-MS/MS）来比较肝硬化和肝癌患者的血清蛋白质组。从 9 名肝硬化患者和 9 名肝癌患者中选择血清进行筛选研究。然后通过 Western blot 选择α-1-酸性糖蛋白（AGP）进行验证。在包括 52 名肝癌患者和 40 名肝硬化患者的独立验证研究中，通过速率散射比浊法测量 AGP。通过接收者操作曲线（ROC）评估其用于从肝硬化中诊断 HCC 的价值。
我们定量和鉴定了 31 种不同的蛋白质，包括 AGP、补体 C4、触珠蛋白、α-1-抗胰蛋白酶前体、α-2-巨球蛋白前体、凝血酶原前体和泛素羧基末端水解酶 44（USP44）等。在验证研究中，肝癌患者（n=52）的血清 AGP 浓度明显高于肝硬化患者（n=40）（P<0.005）。当 AFP 水平低于 500ng/ml 时，AGP 可用于区分 HCC 病例和 LC 患者。AGP 和 AFP 联合的曲线下面积（AUC）分别为 0.834（P<0.0005，95%CI：0.734-0.934）和 0.880（P<0.0005，95%CI，0.789-0.970），高于 AFP 单独（0.538，P=0.604，95%CI：0.386-0.689）。
cICAT 结合基于 LC-MS/MS 的血清蛋白质组分析可用于筛选肝癌的血清生物标志物。AGP 结合 AFP 可辅助 HCC 的诊断。
