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

人血清含有数以千计的蛋白水解性低分子多肽片段(血清多肽)。利用血清多肽组进行癌症诊断的概念已经被提出。当蛋白水解酶和蛋白水解酶抑制物之间的动态平衡被破坏时，就会出现病理性的血清多肽组。我们假设对血清多肽的分析是否具有诊断价值，作为关于哪些分子被破坏的信息，以及在未知的病理条件和弥散性血管内凝血(DIC)中它将采取的病理过程。采用一维凝胶电泳法/基质辅助激光解吸电离质谱仪(1-DE/MS)对1例POEMS(多发性神经病、脏器肿大、内分泌疾病、M蛋白和皮肤改变)综合征患者的早期、DIC前期和DIC前三个阶段的血清多肽组进行了分析。与DIC前相比，DIC阶段出现了大量的多肽片段。此外，我们还鉴定了反式甲状腺素(ALGISPFHEHAEVVFTANDSGPR，m/z 2,451.18)和α1-抗胰蛋白酶(EDPQGDAAQKTDTSHHDQDHPTFN，m/z 2,691.02)片段，它们在DIC阶段与DIC前阶段相比显著增加。对血清多肽组的快速分析可能导致一种诊断方法，该方法可以预测正在进行的蛋白酶激活的病理状态，并有助于决定包括营养支持和药物治疗在内的多种策略。

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.