Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling.
Protein alterations associated with pancreatic cancer and chronic pancreatitis found in human plasma using global quantitative proteomics profiling.
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DOI：
10.1021/pr101148r
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发表时间：
2011-05-06
影响因子：
4.4
通讯作者：
Brentnall, Teresa A.
中科院分区：
文献类型：
--
作者：
Pan, Sheng;Chen, Ru;Crispin, David A.;May, Damon;Stevens, Tyler;McIntosh, Martin W.;Bronner, Mary P.;Ziogas, Argyrios;Anton-Culver, Hoda;Brentnall, Teresa A.
胰腺癌是一种致命的疾病，在可治愈的治疗有效的早期阶段很难诊断。可以改善目前胰腺癌检测的生物标志物将在改善患者管理和生存率方面具有巨大价值。进行了大规模定量蛋白质组学研究，以寻找与胰腺癌相关的血浆蛋白质改变。血浆蛋白质组的巨大复杂性和其中蛋白质浓度的巨大动态范围对血浆的定量全局分析提出了主要挑战。为了应对这些挑战，在蛋白质和肽水平上的多维分级被应用于增强蛋白质组学分析的深度。采用严格的标准，在血浆中鉴定了超过1300种蛋白质，蛋白质浓度为8个数量级。对与胰腺癌相关的差异蛋白质进行了鉴定，并讨论了它们与我们以前研究的胰腺组织和胰液蛋白质组的关系。选择差异表达蛋白质的亚组，使用来自诊断良好的胰腺癌患者、慢性胰腺炎和非胰腺疾病对照的血浆和血清样品的独立队列进行生物标志物测试。使用ELISA方法，将这些候选蛋白中的每一种的性能以CA 19 -9为基准，CA 19 -9是目前胰腺癌血液测试的金标准。TIMP 1和ICAM 1的复合标志物在区分胰腺癌与非胰腺疾病对照和慢性胰腺炎对照方面表现出比CA 19 -9显著更好的性能。此外，蛋白AZGP 1被确定为慢性胰腺炎的生物标志物候选者。血浆蛋白质组学的发现和技术挑战进行了讨论，可能有利于血浆蛋白质组学技术的发展。本研究中鉴定的蛋白候选物为未来的研究提供了生物标志物候选物库。
Pancreatic cancer is a lethal disease that is difficult to diagnose at early stages when curable treatments are effective. Biomarkers that can improve current pancreatic cancer detection would have great value in improving patient management and survival rate. A large scale quantitative proteomics study was performed to search for the plasma protein alterations associated with pancreatic cancer. The enormous complexity of the plasma proteome and the vast dynamic range of protein concentration therein present major challenges for quantitative global profiling of plasma. To address these challenges, multi-dimensional fractionation at both protein and peptide levels was applied to enhance the depth of proteomics analysis. Employing stringent criteria, more than thirteen hundred proteins total were identified in plasma across 8-orders of magnitude in protein concentration. Differential proteins associated with pancreatic cancer were identified, and their relationship with the proteome of pancreatic tissue and pancreatic juice from our previous studies was discussed. A subgroup of differentially expressed proteins was selected for biomarker testing using an independent cohort of plasma and serum samples from well-diagnosed patients with pancreatic cancer, chronic pancreatitis and non-pancreatic disease controls. Using ELISA methodology, the performance of each of these protein candidates was benchmarked against CA19-9, the current gold standard for a pancreatic cancer blood test. A composite marker of TIMP1 and ICAM1 demonstrate significantly better performance than CA19-9 in distinguishing pancreatic cancer from the non-pancreatic disease controls and chronic pancreatitis controls. In addition, protein AZGP1 was identified as a biomarker candidate for chronic pancreatitis. The discovery and technical challenges associated with plasma-based quantitative proteomics are discussed and may benefit the development of plasma proteomics technology in general. The protein candidates identified in this study provide a biomarker candidate pool for future investigations.
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DOI：
10.1186/1756-9966-29-104
发表时间：
2010-08-05
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Chen Y;Yu G;Yu D;Zhu M
通讯作者：
Zhu M
影响因子：
15.8
作者：
Faca VM;Song KS;Wang H;Zhang Q;Krasnoselsky AL;Newcomb LF;Plentz RR;Gurumurthy S;Redston MS;Pitteri SJ;Pereira-Faca SR;Ireton RC;Katayama H;Glukhova V;Phanstiel D;Brenner DE;Anderson MA;Misek D;Scholler N;Urban ND;Barnett MJ;Edelstein C;Goodman GE;Thornquist MD;McIntosh MW;DePinho RA;Bardeesy N;Hanash SM
通讯作者：
Hanash SM
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：
2.9
作者：
Chen, Ru;Pan, Sheng;Brentnall, Teresa A.
通讯作者：
Brentnall, Teresa A.
影响因子：
5.8
作者：
Craig, R;Beavis, RC
通讯作者：
Beavis, RC