Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er RD, Shanghai, 200025, People's Republic of China.
J Gastrointest Surg. 2013 Sep;17(9):1584-91. doi: 10.1007/s11605-013-2182-9. Epub 2013 Jul 19.
Cholangiocarcinoma (CCA) is becoming a common fatal hepatic tumor. Early detection of CCA is hampered by the absence of a sufficiently accurate and noninvasive diagnostic test. Proteomic analysis would be a powerful tool to identify potential biomarkers of this cancer.
This study aims to identify new protein markers that are specific for CCA using proteomic approaches and to evaluate the performance of S100 calcium-binding protein A9 (S100A9) and chaperonin-containing TCR1, subunit 3 (CCTγ) as diagnostic markers for screening test of CCA.
Two-dimensional differential gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to analyze and screen biomarker candidates in the proteomes of five human CCA samples and five healthy control samples. Subsequently, two potential biomarkers, S100A9 and CCTγ, were chosen for validation and analysis by immunohistochemical methods using CCA tissue microarrays.
Twenty protein spots were significantly elevated and five protein spots were downregulated in all patients (p < 0.05). The positive rate was significantly higher in patients with CCA (48 ± 35%) compared with the normal liver control group (5 ± 10%, p < 0.001), the hepatocellular carcinoma group (15 ± 20%, p < 0.001), and the cirrhosis group (12 ± 16%, p < 0.001). A greater proportion of patients with CCA were positive for CCTγ (72 ± 18%) compared with the normal liver control group (43 ± 22%, p < 0.001), the hepatocellular carcinoma group (45 ± 20%, p < 0.001), and the cirrhosis group (39 ± 25%, p < 0.001).
Combined comparative proteomic analysis using 2-D DIGE and MALDI-TOF is an effective method for identifying differentially expressed proteins in CCA tissues. The expression of S100A9 and CCTγ showed promise as novel diagnostic markers for CCA.
胆管癌（CCA）正成为一种常见的致命肝脏肿瘤。由于缺乏足够准确和非侵入性的诊断测试，CCA 的早期检测受到阻碍。蛋白质组学分析将是识别这种癌症潜在生物标志物的有力工具。
本研究旨在使用蛋白质组学方法鉴定新的特异性 CCA 蛋白标志物，并评估 S100 钙结合蛋白 A9（S100A9）和热休克蛋白 10 家族成员 1（HSPH1）作为 CCA 筛查试验的诊断标志物的性能。
二维差异凝胶电泳（2-D DIGE）联合基质辅助激光解吸/电离飞行时间（MALDI-TOF）质谱用于分析和筛选 5 例人 CCA 样本和 5 例健康对照样本的蛋白质组生物标志物候选物。随后，使用 CCA 组织微阵列通过免疫组织化学方法选择两种潜在的生物标志物 S100A9 和 CCTγ 进行验证和分析。
在所有患者中，有 20 个蛋白点明显升高，5 个蛋白点下调（p<0.05）。与正常肝对照组（5%±10%，p<0.001）、肝细胞癌组（15%±20%，p<0.001）和肝硬化组（12%±16%，p<0.001）相比，CCA 患者的阳性率明显更高。与正常肝对照组（43%±22%，p<0.001）、肝细胞癌组（45%±20%，p<0.001）和肝硬化组（39%±25%，p<0.001）相比，更多的 CCA 患者 CCTγ 阳性（72%±18%）。
使用 2-D DIGE 和 MALDI-TOF 的联合比较蛋白质组学分析是鉴定 CCA 组织中差异表达蛋白的有效方法。S100A9 和 CCTγ 的表达有望成为 CCA 的新型诊断标志物。
