Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, 8 Medical Drive, Singapore 117597, Singapore.
J Proteomics. 2013 Dec 6;94:337-45. doi: 10.1016/j.jprot.2013.10.009. Epub 2013 Oct 16.
Mitral regurgitation (MR) is a common valvular lesion frequently caused by mitral valve prolapse (MVP). Surgical intervention in MVP patients with significant MR is predicated on symptoms and measures of left ventricular dysfunction. Because these indicators may be subjective or imprecise, serological biomarkers of disease could be a valuable adjunct to standard evaluation. This study aimed to identify such biomarkers by a proteomics approach. Two pooled plasma samples from 24 MVP subjects with MR (MVP/MR) and 24 non-MVP individuals were treated with the combinatorial peptide ligand library (CPLL) beads prior to iTRAQ labeling and ESI-MS/MS. Lower levels of haptoglobin, platelet basic protein (PBP), and complement component C4b were observed in the MVP/MR as compared to the control sample. These findings were verified by ELISA testing of each of the 24 paired samples, and another 42 matched cases and controls. The AUC values, sensitivities and specificities for (i) haptoglobin, (ii) PBP, (iii) C4b, and (iv) all 3 proteins in combination were (i) 0.813, 76%, 74%; (ii) 0.721, 56%, 77%; (iii) 0.689, 83%, 49%; and (iv) 0.840, 89%, 67%, respectively. In conclusion, haptoglobin, PBP, and C4b are down-regulated in MVP/MR. Their value as serological biomarkers of valvular pathology should be further explored.
We report the first study that performed comparative proteomics of clinical human plasma samples to identify novel diagnostic biomarkers for mitral valve prolapse (MVP) patients with moderate to severe mitral regurgitation (MR). MR is a common valvular lesion that can be complicated by heart failure, sudden death and atrial fibrillation, yet many patients with severe MR are asymptomatic. Our results revealed reduced levels of haptoglobin, platelet basic protein (PBP), and complement component C4b in the MVP/MR patients as compared to the matched control cases. The plasma proteomics findings were subsequently confirmed by ELISA. Each of these candidate biomarkers has a putative role in the pathophysiology of MVP/MR, further supporting their roles in detection and possibly surveillance and prognostication of this disease.
通过蛋白质组学方法来鉴定此类生物标志物。
对 24 例伴有 MR 的 MVP 患者（MVP/MR）和 24 例非 MVP 个体的 2 个混合血浆样本进行处理，采用组合肽配体文库（CPLL）珠，随后进行 iTRAQ 标记和 ESI-MS/MS。与对照样本相比，MVP/MR 中 haptoglobin、血小板碱性蛋白（PBP）和补体 C4b 的水平较低。通过对每个 24 对配对样本和另外 42 例匹配病例和对照进行 ELISA 检测，验证了这些发现。haptoglobin、PBP、C4b 和所有 3 种蛋白联合检测的 AUC 值、敏感性和特异性分别为（i）0.813、76%、74%；（ii）0.721、56%、77%；（iii）0.689、83%、49%；（iv）0.840、89%、67%。
haptoglobin、PBP 和 C4b 在 MVP/MR 中下调。它们作为瓣膜病理的血清学标志物的价值应进一步探讨。
我们报告了第一项进行临床人类血浆样本比较蛋白质组学的研究，以鉴定中度至重度二尖瓣反流（MR）的 MVP 患者的新型诊断生物标志物。MR 是一种常见的瓣膜病变，可导致心力衰竭、猝死和心房颤动，但许多严重 MR 患者无症状。与匹配的对照病例相比，我们的结果显示 MVP/MR 患者的 haptoglobin、血小板碱性蛋白（PBP）和补体 C4b 水平降低。随后通过 ELISA 对血浆蛋白质组学发现进行了确认。这些候选生物标志物中的每一种都在 MVP/MR 的病理生理学中具有潜在作用，进一步支持了它们在检测以及可能的监测和预后方面的作用。
