Quantitative proteomics analysis reveals that proteins differentially expressed in chronic pancreatitis are also frequently involved in pancreatic cancer
Quantitative proteomics analysis reveals that proteins differentially expressed in chronic pancreatitis are also frequently involved in pancreatic cancer
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DOI：
10.1074/mcp.m700072-mcp200
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发表时间：
2007-08-01
影响因子：
7
通讯作者：
Bronner, Mary P.
中科院分区：
文献类型：
--
作者：
Chen, Ru;Brentnall, Teresa A.;Bronner, Mary P.
胰腺癌的有效治疗依赖于早期诊断，这是一项艰巨的挑战。早期胰腺癌诊断生物标志物开发的一个主要障碍是慢性胰腺炎和癌症中潜在生物标志物的双重表达。为了更好地了解潜在蛋白质生物标志物的局限性，我们使用ICAT技术和基于串联质谱的蛋白质组学系统地研究慢性胰腺炎中的蛋白质表达。在慢性胰腺炎中鉴定的116种差异表达蛋白中，大多数生物学过程是对创伤和炎症的反应，这一发现与慢性胰腺炎相关的炎症和组织修复一致。此外，在慢性胰腺炎中鉴定的差异表达蛋白中有40%先前与胰腺癌有关，这表明这两种疾病之间的蛋白表达存在一些共性。生物网络分析进一步确定c-MYC是胰腺癌和慢性胰腺炎中常见的主要调节蛋白。最后选择5个蛋白进行Western blot和免疫组化验证。膜联蛋白A2和胰岛素样生长因子结合蛋白2在癌症中过表达，但在慢性胰腺炎中不表达，这使它们成为胰腺癌有希望的生物标志物候选者。此外，我们的研究证实组织蛋白酶D、整合素β 1和纤溶酶原在胰腺癌和慢性胰腺炎中均过表达。这些蛋白质在慢性胰腺炎和胰腺癌中的积极参与可能会降低这些蛋白质作为胰腺癌生物标志物候选物的特异性。总之，我们的研究为慢性胰腺炎的分子事件提供了一些见解，可能导致这些疾病的诊断和治疗的不同策略。
The effective treatment of pancreatic cancer relies on the diagnosis of the disease at an early stage, a difficult challenge. One major obstacle in the development of diagnostic biomarkers of early pancreatic cancer has been the dual expression of potential biomarkers in both chronic pancreatitis and cancer. To better understand the limitations of potential protein biomarkers, we used ICAT technology and tandem mass spectrometry-based proteomics to systematically study protein expression in chronic pancreatitis. Among the 116 differentially expressed proteins identified in chronic pancreatitis, most biological processes were responses to wounding and inflammation, a finding consistent with the underlining inflammation and tissue repair associated with chronic pancreatitis. Furthermore 40% of the differentially expressed proteins identified in chronic pancreatitis have been implicated previously in pancreatic cancer, suggesting some commonality in protein expression between these two diseases. Biological network analysis further identified c-MYC as a common prominent regulatory protein in pancreatic cancer and chronic pancreatitis. Lastly five proteins were selected for validation by Western blot and immunohistochemistry. Annexin A2 and insulin-like growth factor-binding protein 2 were overexpressed in cancer but not in chronic pancreatitis, making them promising biomarker candidates for pancreatic cancer. In addition, our study validated that cathepsin D, integrin beta 1, and plasminogen were overexpressed in both pancreatic cancer and chronic pancreatitis. The positive involvement of these proteins in chronic pancreatitis and pancreatic cancer will potentially lower the specificity of these proteins as biomarker candidates for pancreatic cancer. Altogether our study provides some insights into the molecular events in chronic pancreatitis that may lead to diverse strategies for diagnosis and treatment of these diseases.