胰腺癌患者血清的比较蛋白质组学研究及其意义

Analysis of pancreatic cancer peripheral blood by comparative proteomics

目的利用比较蛋白质组学方法鉴定胰腺癌早期诊断的差异表达蛋白，筛选出潜在的特异性候选标志物。方法采用双向差异凝胶电泳（2D—DIGE）分离2007年5月至2008年9月收治的20例胰腺癌患者、10例慢性胰腺炎患者和20名健康体检者外周血清蛋白质，利用基质辅助激光解吸电离飞行时间质谱（MALDI—TOF—MS）技术对差异显著的蛋白进行鉴定，并对鉴定出的差异表达蛋白进行Western blot验证。结果成功鉴定出胰腺癌差异表达蛋白补体3（C3）。C3在胰腺癌组织中的灰度比为1．63±0．28，高于正常胰腺的0．65±0．13（t=11．81，P=0．00）和慢性胰腺炎的0．88±0．19（t=9．93，P=0．00）。结论应用2D—DIGE联合MALDF—TOF—MS技术筛选胰腺癌患者外周血清中的特异性生物标志物的方法快速、有效。检测鉴定的差异蛋白质C3可能是胰腺癌早期诊断潜在的血清特异性生物标志物。

Objective To identify protein markers for the early diagnosis of pancreatic cancer by a comparative proteomic method. Methods Comparative analysis on the pancreatic peripheral blood protein profiling from 20 pancreatic cancer patients, 10 chronic pancreatitis patients and 20 cancer-free controls from May 2007 to September 2008 was carried out by two-dimensional fluorescence electrophoresis （2D-DIGE）. Differentially expressed proteins were identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry （MALDI-TOF-MS）. The significance difference proteins were confirmed by Westenl-blot. Results A differentially expressed proteins： complement 3 （C3） was identified. The gray level of C3 in pancreatic cancer tissue, chronic pancreatitis, and normal control group were 1.63 ± 0. 28, 0. 65 ±0. 13 （t = 11.81, P =0. 00） and 0, 88 ±0. 19 （t =9.93, P =0. 00）, respectively. C3 was high expression in pancreatic cancer group compared with normal control group. The expression of C3 was higher in pancreatic cancer group than in chronic pancreatitis group. The high expression of C3 in pancreatic carcinoma was confirmed by Western blot. Conclusions 2D-DIGE and MALDI-TOF-MS technology is a quick, easy and practical method to screen for specific biomarkers in senlm of patients with pancreatic carcinoma. The identified protein C3 in this study may be as specific serum biomarkers of pancreatic carcinoma.