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胰腺癌和胰腺炎的蛋白质组学分析以发现生物标志物

Proteomics Profiling of Pancreatic Cancer and Pancreatitis for Biomarkers Discovery.

作者信息

Sanh N, Fadul H, Hussein N, Lyn-Cook B D, Hammons G, Ramos-Cardona X E, Mohamed K, Mohammed S I

机构信息

Department of Comparative Pathobiology and Purdue University Center for Cancer Research, Purdue University, West Lafayette, USA.

Franklin College, IUPUI- Indiana University Purdue University Indianapolis, Indianapolis, USA.

出版信息

J Cell Sci Ther. 2018;9(4). doi: 10.4172/2157-7013.1000287. Epub 2018 Nov 28.

DOI:10.4172/2157-7013.1000287
PMID:31032145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6481958/
Abstract

Pancreatic cancer is one of the most aggressive malignancies with an increase in incidence predicted, particularly in African Americans. Pancreatic cancer is considered a silent disease with poor prognosis and a lack of early biomarkers for detection. Proteomics has been applied in many diseases for identifying or discovering biomarkers. It has long been suggested that chronic pancreatitis may be a risk factor for developing pancreatic cancer. This study identified proteins that are altered in expression in pancreatic cancer and pancreatitis compared to normal using proteomic technology. Proteins were extracted from laser captured micro-dissected tissues and separated in 2-DPAGE and imaged. The protein profiles of pancreatic cancer and pancreatitis are similar but differed with the protein profile of normal adjacent tissues. Representative proteins, overexpressed in tumor and pancreatitis but not normal tissues, were excised from gels, subjected to in-gel digestion, and analyzed by MALDI-TOF mass spectrometry. Proteins identified included transferrin, ER-60 protein, proapolipoprotein, tropomyosin 1, alpha 1 actin precursor, ACTB protein, and gamma 2 propeptide, aldehyde dehydrogenase 1A1, pancreatic lipase and annexin A1. Several proteins, which were shown in pancreatic cancer, were also observed in pancreatitis samples. Understanding the role of these specific proteins and their mechanistic action will give insights into their involvement in pancreatic cancers.

摘要

胰腺癌是最具侵袭性的恶性肿瘤之一,预计其发病率将会上升,尤其是在非裔美国人中。胰腺癌被认为是一种隐匿性疾病,预后较差,且缺乏早期检测生物标志物。蛋白质组学已应用于许多疾病以识别或发现生物标志物。长期以来,人们一直认为慢性胰腺炎可能是患胰腺癌的一个风险因素。本研究利用蛋白质组学技术,鉴定了与正常组织相比,在胰腺癌和胰腺炎中表达发生改变的蛋白质。从激光捕获显微切割的组织中提取蛋白质,在双向聚丙烯酰胺凝胶电泳中进行分离并成像。胰腺癌和胰腺炎的蛋白质谱相似,但与相邻正常组织的蛋白质谱不同。从凝胶中切下在肿瘤和胰腺炎中过度表达但在正常组织中未过度表达的代表性蛋白质,进行胶内消化,并用基质辅助激光解吸电离飞行时间质谱分析。鉴定出的蛋白质包括转铁蛋白、ER-60蛋白、载脂蛋白前体、原肌球蛋白1、α1肌动蛋白前体、肌动蛋白β蛋白、γ2前肽、醛脱氢酶1A1、胰脂肪酶和膜联蛋白A1。在胰腺癌中出现的几种蛋白质在胰腺炎样本中也有观察到。了解这些特定蛋白质的作用及其作用机制将有助于深入了解它们在胰腺癌中的作用。

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