Laohaviroj Marut, Potriquet Jeremy, Jia Xinying, Suttiprapa Sutas, Chamgramol Yaovalux, Pairojkul Chawalit, Sithithaworn Paiboon, Mulvenna Jason, Sripa Banchob
1 Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
2 WHO Collaborating Centre for Research and Control of Opisthorchiasis (Southeast Asian Liver Fluke Disease), Tropical Disease Research Center (TDRC), Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
Tumour Biol. 2017 Jun;39(6):1010428317705764. doi: 10.1177/1010428317705764.
Cholangiocarcinoma is a primary malignant tumor of the bile duct epithelium. Cholangiocarcinoma is usually detected at an advanced stage when successful treatment is no longer possible. As the tumor originates from the bile duct epithelium, bile is an ideal source of tumor biomarkers for cholangiocarcinoma. In this study, we used a quantitative proteomics approach to identify potential tumor-associated proteins in the bile fluid of six cholangiocarcinoma patients. Three different gross-appearance tumor types were used in the analysis: mass-forming type ( n = 2), periductal infiltrating type ( n = 2), and intraductal growth type ( n = 2). Two bile samples from non-cancerous patients were used as controls. Isobaric labeling, coupled with Tandem mass spectrometry, was used to quantify protein levels in the bile of cholangiocarcinoma and control patients. In all, 63 proteins were significantly increased in cholangiocarcinoma bile compared to normal bile. Alpha-1-antitrypsin was one of the overexpressed proteins that increased in cholangiocarcinoma bile samples. Immunohistochemical analysis revealed that alpha-1-antitrypsin was detected in 177 (50%) of 354 cholangiocarcinoma tissues from our Tissue Bank. Immunoblotting of 54 cholangiocarcinoma bile samples showed that alpha-1-antitrypsin was positive in 38 (70%) samples. Fecal enzyme-linked immunosorbent assay showed that alpha-1-antitrypsin level was able to distinguish cholangiocarcinoma patients from normal individuals. In conclusion, alpha-1-antitrypsin is a potential marker for early diagnosis of cholangiocarcinoma.
胆管癌是胆管上皮的原发性恶性肿瘤。胆管癌通常在晚期才被发现，此时已无法进行成功治疗。由于肿瘤起源于胆管上皮，胆汁是胆管癌肿瘤生物标志物的理想来源。在本研究中，我们采用定量蛋白质组学方法，在6例胆管癌患者的胆汁中鉴定潜在的肿瘤相关蛋白。分析中使用了三种不同大体外观的肿瘤类型：肿块形成型（n = 2）、导管周围浸润型（n = 2）和导管内生长型（n = 2）。来自非癌症患者的两份胆汁样本用作对照。采用等压标记结合串联质谱法，对胆管癌患者和对照患者胆汁中的蛋白质水平进行定量。与正常胆汁相比，胆管癌胆汁中共有63种蛋白质显著增加。α-1-抗胰蛋白酶是胆管癌胆汁样本中表达上调的蛋白质之一。免疫组织化学分析显示，在我们组织库的354例胆管癌组织中，有177例（50%）检测到α-1-抗胰蛋白酶。对54例胆管癌胆汁样本进行免疫印迹分析，结果显示38例（70%）样本中α-1-抗胰蛋白酶呈阳性。粪便酶联免疫吸附试验表明，α-1-抗胰蛋白酶水平能够区分胆管癌患者和正常个体。总之，α-1-抗胰蛋白酶是胆管癌早期诊断的潜在标志物。
