Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Proteomics. 2011 Dec;11(23):4551-8. doi: 10.1002/pmic.201100264. Epub 2011 Oct 28.
Pancreatic cancer (PC) is one of the most lethal malignancies and disease-specific biomarkers are desperately needed for better diagnosis, prognosis, monitoring treatment efficacy and for accelerating the development of novel targeted therapeutics. Being an advanced stage manifestation and a proximal fluid in contact with cancer tissues, the ascitic fluid presents itself as a promising rich source of biomarkers. Herein, we present a comprehensive proteomic analysis of pancreatic ascitic fluid. To fractionate the complex ascites proteome, we adopted a multi-dimensional chromatographic approach that included size-exclusion, ion-exchange and lectin-affinity chromatographic techniques. Our detailed proteomic analysis with high-resolution Orbitrap(®) mass spectrometer resulted in the identification of 816 proteins. We followed rigorous filtering criteria that consisted of PC-specific information obtained from three publicly available databases (Oncomine, Protein Atlas and Unigene) to segregate 20 putative biomarker candidates for future validation. Since these proteins are of membranous and extra-cellular origin, most are glycosylated, and many of them are over-expressed in cancer tissues, the probability of these proteins entering the peripheral blood circulation is high. Their validation as serological PC biomarkers in the future is highly warranted.
胰腺癌（PC）是最致命的恶性肿瘤之一，迫切需要疾病特异性生物标志物来改善诊断、预后、监测治疗效果，并加速新型靶向治疗的发展。由于腹水是晚期表现和与癌症组织直接接触的近端液体，因此它是一种很有前途的生物标志物丰富来源。在此，我们对胰腺腹水进行了全面的蛋白质组学分析。为了对复杂的腹水蛋白质组进行分离，我们采用了多维色谱方法，包括分子筛、离子交换和凝集素亲和色谱技术。我们使用高分辨率 Orbitrap（®）质谱仪进行详细的蛋白质组学分析，鉴定出 816 种蛋白质。我们遵循了严格的过滤标准，该标准包括从三个公开可用的数据库（Oncomine、Protein Atlas 和 Unigene）获得的 PC 特异性信息，以分离 20 种有前途的生物标志物候选物用于未来验证。由于这些蛋白质来源于膜和细胞外，大多数是糖基化的，并且其中许多在癌症组织中过度表达，因此这些蛋白质进入外周血液循环的可能性很高。将来验证它们作为血清学 PC 生物标志物是非常必要的。
