Sriwanitchrak Pramote, Viyanant Vithoon, Chaijaroenkul Wanna, Srivatanakul Petcharin, Gram Hans Rudi, Eursiddhichai Veerachai, Na-Bangchang Kesara
Thailand Center of Excellence on Drug Discovery Development, Thammasat University, Pathumthani, Thailand.
Asian Pac J Cancer Prev. 2011;12(6):1503-10.
Cholangiocarcinoma (CCA) is a rare but devastating neoplasm that accounts for about 3% of all gastrointestinal cancers and about 15% of all primary liver cancers worldwide. The lack of early detection and limited therapeutic options are major problems in controlling CCA. The current study attempted to identify novel serum markers which can substitute the carbohydrate antigen CA19-9, or can improve, when measured together, the diagnostic accuracy of CA19-9. Differentially expressed proteins in pooled and individual plasma samples obtained from patients with CCA and control subjects (10 each) were identified by using two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MALDI-TOF). Out of a total of 21 protein spots separated and identified, five spots were found to be up-regulated in plasma from CCA patients. The up-regulation of α1-antitrypsin (AP1) was observed in all of the ten samples from CCA patients with protein intensity significantly higher than control subjects. Based on results of binary logistic regression analysis of the three serum biomarkers (CA19-9, AP1 and α-fetoprotein: AFP), serum levels of at least CA19-9 together with AP1 were the minimum requirement to obtain prediction accuracy of greater than 80% in a battery test for diagnosis of CCA. However, in order to obtain high predictability of 100% or approaching, an addition of at least one of the three liver function enzymes (alkaline phosphatase: ALP; aspartase transaminase: AST; alanine trasaminase: ALT) is required. Serum biomarkers may be a useful diagnostic or prognostic monitoring tool for CCA. Further evaluation of larger number samples is needed to support their applicability in a clinical setting as diagnostic and prognostic tools. Determination of clinical utility of these marker models in early diagnosis of CCA requires study in animal models with disease progression.
胆管癌（CCA）是一种罕见但极具破坏性的肿瘤，约占全球所有胃肠道癌症的3%，占所有原发性肝癌的15%左右。缺乏早期检测手段以及治疗选择有限是控制CCA的主要问题。本研究试图鉴定可替代糖类抗原CA19-9，或与CA19-9一起检测时能提高其诊断准确性的新型血清标志物。通过二维凝胶电泳（2-DE）和基质辅助激光解吸电离飞行时间质谱（MALDI-TOF），鉴定了从CCA患者和对照受试者（各10例）获得的混合血浆样本及个体血浆样本中差异表达的蛋白质。在总共分离并鉴定的21个蛋白点中，发现有5个点在CCA患者血浆中上调。在所有10例CCA患者样本中均观察到α1-抗胰蛋白酶（AP1）上调，其蛋白强度显著高于对照受试者。基于对三种血清生物标志物（CA19-9、AP1和甲胎蛋白：AFP）的二元逻辑回归分析结果，在CCA诊断的联合检测中，至少CA19-9与AP1的血清水平是获得大于80%预测准确性的最低要求。然而，为了获得100%或接近100%的高预测性，则需要添加三种肝功能酶（碱性磷酸酶：ALP；天冬氨酸转氨酶：AST；丙氨酸转氨酶：ALT）中的至少一种。血清生物标志物可能是CCA有用的诊断或预后监测工具。需要进一步评估更多样本，以支持其在临床环境中作为诊断和预后工具的适用性。确定这些标志物模型在CCA早期诊断中的临床效用需要在疾病进展的动物模型中进行研究。
