The assignments were based on GO consortium

The assignments were based on GO consortium. Many of the proteins identified in pancreatic juice were enzymes (catalytic activity, 35%). in pancreatitis juice by at least 2-fold compared with normal pancreatic juice. Of these 27 differentially expressed proteins in pancreatitis, 9 proteins were also differentially expressed in the pancreatic juice from pancreatic cancer patient. Conclusions Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer. strong class=”kwd-title” Keywords: pancreatic juice, pancreatitis, ICAT, biomarker, pancreatic cancer, proteomics Pancreatic A 740003 cancer is usually a highly lethal disease.1,2 The death rate A 740003 nearly matches the incidence because the diagnosis usually occurs late, after metastases have occurred, and the only chance for a cure (ie, surgical excision) has been eliminated. The problem of early diagnosis is usually complicated by the obscure location of the pancreas, the absence of reliable symptoms, and the insensitivity and expense of current assessments. Better methods of detecting early stages of cancer or precancerous lesions are needed. In the efforts to develop biomarkers for the early detection of pancreatic cancer, one of the problems is the false-positive involvement of pancreatitis patients. Pancreatitis is an inflammatory condition of the pancreas that shares many molecular features with pancreatic cancer. Thus, biomarkers present in the setting of pancreatic cancer frequently occur in pancreatitis, providing an unacceptably low level of specificity for screening. It is therefore important to understand the proteins that underlie pancreatitis, as they could be a source of false-positive biomarkers for pancreatic cancer. Moreover, chronic CCND2 pancreatitis is usually risk factor for eventual neoplastic progression; thus, understanding the proteins involved in both diseases may yield some insights into the mechanisms that link these events. Recently, there has been substantial interest in applying proteomic methods for the discovery of new targets for therapeutics and new biomarkers for diagnosis and early A 740003 detection.3 In particular, quantitative proteomics has enabled researchers to use a combination of biochemistry, biology, and bioinformatics to detect proteins that are differentially expressed in cancer. In pancreatic cancer, recent studies using proteomics approach have focused on pancreatic cancer tissues.4C6 However, from a biomarkers standpoint, pancreatic juice is an excellent starting specimen for the identification of protein biomarkers. Pancreatic juice is usually a rich source for cancer-specific proteins because the highly proliferative cancer cells are shed into the juice, as they undergo cellular turnover and degradation. 7 Pancreatic juice was extensively studied in late 1970s and 1980s, primarily by early 2-dimensional electrophoresis analyses, which led to the discovery and description of several pancreatic enzymes.8C12 Recently, Gronborg and colleagues13 used a mass spectrometry-based proteomic approach for the analysis of pancreatic juice which used 1-dimensional electrophoresis and liquid chromatography (LC) tandem mass spectrometry (MS/MS). We previously used an isotope-coded affinity tag (ICAT)Cbased quantitative proteomic approach to identify and characterize potential biomarkers from pancreatic cancer juice.14 A total of 30 proteins were identified that exhibited greater than 2-fold abundance change in pancreatic cancer juice compared with normal pancreatic juice. Given the false-positive role of pancreatitis in pancreatic cancer, it is important to discover possible pancreatitis specific proteins that can be used to differentiate pancreatic cancer and pancreatitis. In addition, discovery of the proteins in pancreatitis could help identify proteins that might contribute to false-positive findings of pancreatic cancer. Isotope-coded affinity tag (ICAT) technology provides a comprehensive approach for quantitative proteomic analysis.15,16 This methodology demonstrates a significant improvement over gel-based methods A 740003 in identifying low-abundant proteins, and it minimizes problems associated with solubility and extremes of pH. 17 In this study, we used ICAT technology to perform comprehensive quantitative protein profiling of the pancreatitis juice. We performed the analyses by comparing pooled normal pancreatic juice with pancreatic juice from a chronic pancreatitis patient. Identification and quantification of the proteins from pancreatic juice were accomplished by differentially labeling the target proteins (pancreatitis) with heavy ICAT reagents and the normal comparator proteins with light ICAT reagents. The isotopically labeled proteins were then combined, purified,.