Diagnostic value of peptidome analyses for protease activated pathological conditions beyond cancer diagnosis

人血清含有成千上万的蛋白水解衍生的低分子量肽片段（血清肽穹）。利用血清肽球进行癌症诊断的概念已经发展起来。当蛋白酶和蛋白酶抑制剂之间的稳态平衡被破坏时，就会出现病理性血清肽丘。我们假设分析血清肽肽是否具有诊断价值，作为哪些分子被破坏的信息，以及在未知病理条件和弥散性血管内凝血（DIC）中它将采取的病理过程。我们采用基于一维凝胶电泳/基质辅助激光解吸/电离质谱（1-DE/MS）的快速定量方法，分析了1例难治性疾病POEMS（多发性神经病变、器官肿大、内分泌病变、M蛋白和皮肤变化）综合征患者3个阶段（早期、DIC前期和DIC阶段）的血清肽水平。与DIC前期相比，DIC阶段出现了大量的肽片段。此外，我们发现转甲状腺素片段（ALGISPFHEHAEVVFTANDSGPR, m/z 2,451.18）和α1-抗胰蛋白酶片段（EDPQGDAAQKTDTSHHDQDHPTFN, m/z 2,691.02）在DIC阶段与DIC前期相比显著增加。对血清肽肽的快速分析可能会导致一种诊断方法，可以预测正在进行的蛋白酶激活的病理状况，并有助于决定包括营养支持和药物治疗在内的多边策略。

Human serum contains thousands of proteolytically derived low-molecular-weight peptide fragments (serum peptidome). The concept of utilizing the serum peptidome for cancer diagnosis has been developed. A pathological serum peptidome appears when the homeostatic balance between proteases and protease inhibitors is disrupted. We hypothesize if analyses of the serum peptidome are of diagnostic value as information on which molecules are disrupted, and the pathological course it will take in unknown pathological conditions and disseminated intravascular coagulation (DIC). We analyzed the serum peptidome in 3 stages (early stage, pre-DIC and DIC stages) in one patient with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein and skin changes) syndrome, an intractable disease with unknown pathology, using a 1-dimensional gel electrophoresis/ matrix-assisted laser desorption/ionization-mass spectrometry (1-DE/MS)-based rapid quantitative approach. A very large number of peptide fragments appeared in the DIC stage, compared to pre-DIC. In addition, we identified fragments of transthyretin (ALGISPFHEHAEVVFTANDSGPR, m/z 2,451.18) and α1-antitrypsin (EDPQGDAAQKTDTSHHDQDHPTFN, m/z 2,691.02) that significantly increased in the DIC stage, compared to those in the pre-DIC stage. Rapid analyses of the serum peptidome may lead to a diagnostic method that can predict on-going protease activated pathological conditions and help to decide on multilateral strategies including nutritional support and drug therapy.