慢性胰腺炎和胰腺腺癌的蛋白质组学分析
Proteomic analysis of chronic pancreatitis and pancreatic adenocarcinoma.
作者信息
Crnogorac-Jurcevic Tatjana, Gangeswaran Rathi, Bhakta Vipul, Capurso Gabriele, Lattimore Samuel, Akada Masanori, Sunamura Makoto, Prime Wendy, Campbell Fiona, Brentnall Teresa A, Costello Eithne, Neoptolemos John, Lemoine Nicholas R
机构信息
Molecular Oncology Unit, Cancer Research UK, Barts and The London School of Medicine and Dentistry, John Vane Science Centre, Charterhouse Square, London, United Kingdom.
出版信息
Gastroenterology. 2005 Nov;129(5):1454-63. doi: 10.1053/j.gastro.2005.08.012.
BACKGROUND & AIMS: Markers to differentiate among pancreatic adenocarcinoma, chronic pancreatitis, and normal pancreas would be of significant clinical utility. This study was therefore designed to analyze the proteome of such specimens and identify new candidate proteins for differential diagnosis.
METHODS
A PowerBlot analysis with more than 900 well-characterized antibodies was performed with tissue specimens from patients with chronic pancreatitis, pancreatic adenocarcinoma, and normal pancreas. Differential expression of selected proteins was confirmed on a larger scale by quantitative reverse transcription-polymerase chain reaction and immunohistochemistry using tissue arrays.
RESULTS
A total of 30 and 102 proteins showed significant deregulation between normal pancreas when compared with chronic pancreatitis and pancreatic adenocarcinoma, respectively, and although a substantial proportion were found similarly dysregulated in both chronic pancreatitis and pancreatic adenocarcinoma, several proteins were identified as potential disease-specific markers.
CONCLUSIONS
A large number of proteins are differentially expressed in chronic pancreatitis and pancreatic adenocarcinoma compared with normal pancreas. Among these, expression analysis of UHRF1, ATP7A, and aldehyde oxidase 1 in combination could potentially provide a useful additional diagnostic tool for fine-needle aspirated or cytological specimens obtained during endoscopic investigations.
背景与目的
能够区分胰腺腺癌、慢性胰腺炎和正常胰腺的标志物具有重要的临床应用价值。因此,本研究旨在分析此类标本的蛋白质组,并鉴定用于鉴别诊断的新候选蛋白。
方法
使用来自慢性胰腺炎、胰腺腺癌患者及正常胰腺的组织标本,采用PowerBlot分析法,用900多种特征明确的抗体进行检测。通过定量逆转录-聚合酶链反应和使用组织芯片的免疫组织化学方法,在更大规模上证实所选蛋白质的差异表达。
结果
与慢性胰腺炎相比,正常胰腺与慢性胰腺炎之间共有30种蛋白质显示出显著失调;与胰腺腺癌相比,正常胰腺与胰腺腺癌之间共有102种蛋白质显示出显著失调。虽然在慢性胰腺炎和胰腺腺癌中发现相当一部分蛋白质的失调情况相似,但仍有几种蛋白质被鉴定为潜在的疾病特异性标志物。
结论
与正常胰腺相比,慢性胰腺炎和胰腺腺癌中有大量蛋白质存在差异表达。其中,联合分析UHRF1、ATP7A和醛氧化酶1的表达情况,可能为内镜检查时获取的细针穿刺或细胞学标本提供一种有用的辅助诊断工具。