Identification of serum proteins involved in pancreatic cancer cachexia
Identification of serum proteins involved in pancreatic cancer cachexia
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DOI：
10.1016/j.lfs.2010.11.011
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发表时间：
2011-01-31
期刊：
影响因子：
6.1
通讯作者：
Werner, Jens
中科院分区：
文献类型：
--
作者：
Felix, Klaus;Fakelman, Frederik;Werner, Jens
目的：恶病质的治疗需要药物干预，这反过来又需要了解介质和过程。在胰腺癌中特异性表达并分泌到血液循环中的恶病质标志物尚未确定。我们的研究的目的是调查与恶病质相关的血清蛋白质谱和蛋白质改变，并确定潜在的疾病蛋白质生物标志物指示这种syndrome.Main方法：恶病质和非恶病质患者进行胰腺癌（PaCa）手术和对照组的血清样品进行了调查，表面增强激光解吸/电离飞行时间质谱（SELDI-TOF-MS）。通过蛋白质分级分离、色谱纯化步骤、凝胶电泳和质谱分析相结合，确定了检测到的鉴别标记的身份。主要发现：使用Cu-IMAC阵列和基于CM-10阵列的SELDI-TOF-MS。CiphergenExpress分析揭示了四种疾病相关蛋白质特征（38559 Da、9138 Da、8925 Da和3358 Da），其分别升高了2.3、1.7、1.4和1.4倍。锌-α 2-糖蛋白（ZAG）、载脂蛋白apo C-II和apo C-III以及胰高血糖素样肽-1（GLP-1）被确定为PaCa相关恶病质综合征的标志物。ZAG水平进行了额外的评价，血清和组织样本中的ELISA和免疫组化和获得的数据证实了SELDI-TOF-MS results.Significance：所确定的蛋白质可以常规和可靠地测量在患者的血清中，并提供了一个优雅的非侵入性的恶病质胰腺癌患者的早期诊断方法。控制ZAG和GLP-1活性可能有益于癌症和恶病质诱导的病症的管理。(C)2010年爱思唯尔公司All rights reserved.
Aims: Treatment of cachexia requires pharmacological intervention which, in turn, requires knowledge of the mediators and processes. Cachexia markers that are specifically expressed in pancreatic cancer and secreted into the blood circulation have yet to be identified. The aim of our study was to investigate the serum protein profiles and protein alterations associated with cachexia and to identify potential disease protein biomarkers indicative for this syndrome.Main methods: Serum samples from cachectic and non-cachectic patients undergoing pancreatic cancer (PaCa) surgery and controls were investigated by Surface Enhanced Laser Desorption/lonization Time-of-Flight Mass Spectrometry (SELDI-TOF-MS). The identity of detected discriminatory markers was determined by a combination of protein fractionation, chromatographic purification steps, gel electrophoresis, and mass spectrometry.Key findings: Using Cu-IMAC array and CM-10 array based SELDI-TOF-MS. we identified eleven up- and four down-regulated proteins associated with cachexia. CiphergenExpress analysis revealed four disease-associated protein features (38559 Da, 9138 Da, 8925 Da and 3358 Da) that were elevated by a factor of 2.3, 1.7, 1.4 and 1.4, respectively. Zinc-alpha 2-glycoprotein (ZAG), apolipoproteins apo C-II and apo C-III and glucagon-like peptide-1 (GLP-1) were identified as markers for PaCa-associated cachexia syndrome. ZAG levels were additionally evaluated in serum and tissue samples by ELISA and immunohistochemistry and the obtained data confirmed the SELDI-TOF-MS results.Significance: The identified proteins could be routinely and reliably measured in the serum of patients and provide an elegant non-invasive approach for early diagnosis of cachectic pancreatic cancer patients. Controlling ZAG and GLP-1 activity could be beneficial in the management of cancers and cachexia-induced conditions. (C) 2010 Elsevier Inc. All rights reserved.