基于质谱鉴定的肝癌标志物的血清iTRAQ分析

iTRAQ analysis of serum biomarkers of hepatocellular carcinoma based on mass spectrometry

目的:采用核素标记相对和绝对定量(isobaric tags for relative and absolute quantitation,iTRAQ)技术分析已报道的基于质谱鉴定的肝癌标志物在血清中的表达水平。方法:通过PubMed查阅2003年1月-2010年8月发表的,采用差异蛋白筛选结合基质辅助激光解析/电离-飞行时间质谱技术(matrix-assisted laser desorption/ionization time-of-fight mass spectrometry,MALDI-TOF-MS)鉴定的有关肝癌生物标志物的文献;同时运用iTRAQ标记技术结合MALDI-TOF-MS串联质谱技术,对20例肝癌患者与20例健康对照的血清进行差异蛋白组学分析。将文献报道的肝癌标志物数据与肝癌血清差异蛋白组学数据进行比对。结果:通过文献检索共获得符合要求的文献22篇,涉及肝癌相关标志物262个。肝癌血清差异蛋白组筛选出表达有显著差异的蛋白51个,其中在肝癌血清中高表达差异蛋白23个,低表达差异蛋白28个;与文献报道吻合的标志物8个,其中与文献报道表达水平一致的差异蛋白为6个[α-1-抗胰蛋白酶(alpha-1-antitrypsin,AAT)、载脂蛋白E(apolipoprotein E,APOE)、蛋白血浆铜蓝蛋白(ceruloplasmin,CP)、甲胎蛋白(alpha fetoprotein,AFP)、补体C3(complement C3,C3)和血清淀粉状蛋白P片段(serum amyloid P-component,APCS)]。结论:血清中鉴定获得的6个与文献报道一致的差异蛋白可能是潜在肝癌标志物,值得进一步深入探讨研究。

Objective： The technique of isobaric tags for relative and absolute quantitation （iTRAQ） was used to analyze the expression levels of serum biomarkers of hepatocellular carcinoma （HCC） based on mass spectrometry. Methods： The literature about HCC biomarkers identified by screening of differential protein expression combined with matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry （MALDI-TOF-MS） published between January 2003 and August 2010 were selected by searching PubMed database. Screening for serum differential proteins was performed in 20 HCC patients and 20 healthy volunteers by using iTRAQ labeling and MALDI-TOF-MS. The reported data of HCC biomarkers were compared with the screening results of serum differential protein expression in HCC. Results： Twenty-two pieces of eligible literature were obtained by information retrieval, involving 262 HCC biomarkers. Fifty-one proteins were identified having differential expression by using screening of serum differential protein expression in HCC. In the 51 proteins, the expression level of 23 proteins was high, while the expression level of 28 proteins was low. Eight differential proteins which were identified by screening, were in accordance with literature reports, and 6 differential proteins （alpha-1-antitrypsin, apolipoprotein E, ceruloplasmin, alpha fetoprotein, complement C3 and serum amyloid P-component） had the similar expression levels in accordance with literature reports. Conclusion： Six differential proteinsidentified in serum are the same as reported in the literatures, and these proteins may become potential HCC biomarkers. There is a need for further study to explore these differential proteins.