Proteomics portrait of archival lesions of chronic pancreatitis.
Proteomics portrait of archival lesions of chronic pancreatitis.
复制标题
慢性胰腺炎档案病变的蛋白质组学肖像。
DOI：
10.1371/journal.pone.0027574
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Brentnall TA
中科院分区：
文献类型：
--
作者：
Pan S;Chen R;Stevens T;Bronner MP;May D;Tamura Y;McIntosh MW;Brentnall TA
慢性胰腺炎是胰腺的慢性炎症性疾病。病因是多方面的，但都会导致进行性疤痕形成和胰腺功能丧失。早期诊断困难；对这种进行性疾病背后的分子事件的理解是有限的。在这项研究中，我们与正常胰腺和胰腺癌相比，研究了与轻度和重度慢性胰腺炎相关的差异蛋白。使用“无标记”比较方法对来自正常胰腺 (NL)、轻度慢性胰腺炎 (MCP)、严重慢性胰腺炎 (SCP) 和胰腺导管腺癌 (PDAC) 五个特征良好的标本的石蜡包埋福尔马林固定组织进行蛋白质组分析。我们的结果表明，差异蛋白的数量随着疾病严重程度（从轻度到重度慢性胰腺炎）的增加而大幅增加，而失调蛋白的数量在胰腺腺癌中最高。与慢性胰腺炎和癌症相关的重要功能组和生物过程包括腺泡细胞分泌蛋白、胰腺纤维化/星状细胞活化、糖蛋白和炎症蛋白。选择三种差异蛋白进行免疫组化验证，包括胶原14A1、lumican和versican。进一步的经典通路分析显示，急性期反应信号、凝血酶原激活通路、胰腺纤维化/胰腺星状细胞激活通路是慢性胰腺炎中最重要的通路，而代谢相关通路是胰腺癌中最重要的通路。我们的研究揭示了一组差异表达的蛋白质和相关途径，可能有助于揭示慢性胰腺炎的发病机制以及与慢性胰腺炎和胰腺腺癌相关的常见分子事件。
Chronic pancreatitis is a chronic inflammatory disorder of the pancreas. The etiology is multi-fold, but all lead to progressive scarring and loss of pancreatic function. Early diagnosis is difficult; and the understanding of the molecular events that underlie this progressive disease is limited. In this study, we investigated differential proteins associated with mild and severe chronic pancreatitis in comparison with normal pancreas and pancreatic cancer. Paraffin-embedded formalin-fixed tissues from five well-characterized specimens each of normal pancreas (NL), mild chronic pancreatitis (MCP), severe chronic pancreatitis (SCP) and pancreatic ductal adenocarcinoma (PDAC) were subjected to proteomic analysis using a “label-free” comparative approach. Our results show that the numbers of differential proteins increase substantially with the disease severity, from mild to severe chronic pancreatitis, while the number of dysregulated proteins is highest in pancreatic adenocarcinoma. Important functional groups and biological processes associated with chronic pancreatitis and cancer include acinar cell secretory proteins, pancreatic fibrosis/stellate cell activation, glycoproteins, and inflammatory proteins. Three differential proteins were selected for verification by immunohistochemistry, including collagen 14A1, lumican and versican. Further canonical pathway analysis revealed that acute phase response signal, prothrombin activation pathway, and pancreatic fibrosis/pancreatic stellate cell activation pathway were the most significant pathways involved in chronic pancreatitis, while pathways relating to metabolism were the most significant pathways in pancreatic adenocarcinoma. Our study reveals a group of differentially expressed proteins and the related pathways that may shed light on the pathogenesis of chronic pancreatitis and the common molecular events associated with chronic pancreatitis and pancreatic adenocarcinoma.
登录
查看更多内容
影响因子：
3.4
作者：
Deutsch, Eric W.;Mendoza, Luis;Shteynberg, David;Farrah, Terry;Lam, Henry;Tasman, Natalie;Sun, Zhi;Nilsson, Erik;Pratt, Brian;Prazen, Bryan;Eng, Jimmy K.;Martin, Daniel B.;Nesvizhskii, Alexey I.;Aebersold, Ruedi
通讯作者：
Aebersold, Ruedi
影响因子：
6.4
作者：
Cui, Yazhou;Wu, Jianmei;Han, Jinxiang
通讯作者：
Han, Jinxiang
影响因子：
5.8
作者：
Bellew, Matthew;Coram, Marc;McIntosh, Martin
通讯作者：
McIntosh, Martin
影响因子：
7
作者：
Chen, Ru;Brentnall, Teresa A.;Bronner, Mary P.
通讯作者：
Bronner, Mary P.
影响因子：
5.8
作者：
Craig, R;Beavis, RC
通讯作者：
Beavis, RC