Hanas Jay S, Hocker James R, Cheung John Y, Larabee Jason L, Lerner Megan R, Lightfoot Stan A, Morgan Daniel L, Denson Kent D, Prejeant Kristi C, Gusev Yuiry, Smith Brenda J, Hanas Rushie J, Postier Russell G, Brackett Daniel J
Department of Biochemistry & Molecular Biology, University of Oklahoma Health Science Center, Oklahoma City, OK, USA.
Pancreas. 2008 Jan;36(1):61-9. doi: 10.1097/mpa.0b013e3180d0a738.
The aim of this study is to identify biomarkers in sera of pancreatic cancer patients using mass spectrometry (MS) approaches.
Sera from patients diagnosed with pancreatic adenocarcinoma and sera from normal volunteers were subjected to gel electrophoresis to resolve and quantify differences in protein levels. Protein bands that differed quantitatively were digested with trypsin, and peptides were identified by electrospray ionization (ESI) ion-trap tandem MS. Mass spectra were also collected directly from pancreatic cancer sera as well as healthy control sera using ESI-MS.
Three large-mass proteins were found to be elevated in pancreatic cancer sera versus normal sera, alpha-2 macroglobulin, ceruloplasmin, and complement 3C. Complement 3C is a major regulator of inflammatory responses. The ESI-MS of human pancreatic cancer sera versus normal sera revealed greater heterogeneity in cancer sera than control sera, especially in the low-mass region. Bootstrapping statistical analysis identified 20 low-mass serum peaks that correlated with control sera and 20 different peaks that correlated with pancreatic cancer sera.
The fact that inflammation-sensitive proteins were identified as increased in pancreatic cancer sera supports the hypothesis that inflammatory-driven processes are involved in pancreatic carcinogenesis. Liquid ESI-MS analyses of sera hold promise for future pancreatic cancer blood tests as well as for understanding mechanisms of pancreatic carcinogenesis. The variability observed between the low-mass regions of normal versus pancreatic cancer spectra may aid in diagnosis and therapy.
本研究旨在采用质谱（MS）方法鉴定胰腺癌患者血清中的生物标志物。
将胰腺癌患者的血清和正常志愿者的血清进行凝胶电泳，以解析和定量蛋白质水平的差异。对定量上有差异的蛋白条带用胰蛋白酶进行消化，通过电喷雾电离（ESI）离子阱串联质谱鉴定肽段。还使用ESI-MS直接从胰腺癌血清以及健康对照血清中采集质谱。
发现与正常血清相比，胰腺癌血清中有三种大分子蛋白升高，即α-2巨球蛋白、铜蓝蛋白和补体3C。补体3C是炎症反应的主要调节因子。与正常血清相比，人胰腺癌血清的ESI-MS显示癌症血清中的异质性高于对照血清，尤其是在低分子量区域。自展统计分析确定了20个与对照血清相关的低分子量血清峰和20个与胰腺癌血清相关的不同峰。
在胰腺癌血清中鉴定出炎症敏感蛋白增加这一事实支持了炎症驱动过程参与胰腺癌发生的假说。血清的液相ESI-MS分析对未来的胰腺癌血液检测以及理解胰腺癌发生机制具有前景。正常光谱与胰腺癌光谱低分子量区域之间观察到的变异性可能有助于诊断和治疗。
