INSERM, U744, Lille, France.
Proteomics Clin Appl. 2010 Jul;4(6-7):654-73. doi: 10.1002/prca.200900178. Epub 2010 Mar 24.
Depletion of major blood proteins is one of the most promising approaches to accessing low abundance biomarkers for proteomics studies. The use of combinatorial peptide ligand library (CPLL) for accessing these low abundance proteins in plasma from patients with a myocardial infarction (MI) was tested to identify candidate protein biomarkers of left ventricular remodeling (LVR).
Serial blood samples of MI patients followed for one year (at inclusion, 1 month, 3 months, and 1 year) were treated with CPLL and analyzed by SELDI-TOF-MS.
The use of CPLL increased resolution, with loss of most abundant plasma proteins, reproducibly and improved the intensity of low-abundance proteins. Longitudinal information allowed us to reduce by 55% the final number of peaks identified as significantly modulated throughout the 1-year follow-up after MI. Interestingly, 19 of the 26 peaks finally selected were detected only in samples treated from CPLL. The 2777 m/z peak, found in less elevated level in high remodeling patients, was identified as being DAHKSEVAHR FKDLGEENFKALVL, the N-terminal peptide (24-48 aa) generated from albumin by pepsin cleavage.
This finding shows the potential of CPLL in accessing low-abundance proteins to select and identify candidate biomarkers in patients with LVR.
耗尽主要血液蛋白是获取蛋白质组学研究中低丰度生物标志物的最有前途的方法之一。本研究旨在测试组合肽配体文库 (CPLL) 是否可用于从心肌梗死 (MI) 患者的血浆中获取这些低丰度蛋白质，以鉴定左心室重构 (LVR) 的候选蛋白生物标志物。
对随访 1 年的 MI 患者的连续血液样本（纳入时、1 个月、3 个月和 1 年）进行 CPLL 处理，并通过 SELDI-TOF-MS 进行分析。
CPLL 的使用可增加分辨率，丢失大多数丰富的血浆蛋白质，具有重现性，并提高低丰度蛋白质的强度。纵向信息使我们能够将 MI 后 1 年随访期间被鉴定为显著调节的峰的最终数量减少 55%。有趣的是，最终选择的 26 个峰中的 19 个仅在 CPLL 处理的样本中检测到。2777 m/z 峰在高重构患者中的水平较低，被鉴定为 DAHKSEVAHR FKDLGEENFKALVL，这是胃蛋白酶切割白蛋白产生的 N 端肽（24-48 aa）。
这一发现表明 CPLL 具有从低丰度蛋白质中获取低丰度蛋白质的潜力，可用于选择和鉴定 LVR 患者的候选生物标志物。
