Serum proteomic predicts effectiveness and reveals potential biomarkers for complications in liver transplant patients
Serum proteomic predicts effectiveness and reveals potential biomarkers for complications in liver transplant patients
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血清蛋白质组学预测肝移植患者并发症的有效性并揭示潜在的生物标志物
DOI：
10.18632/aging.103381
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发表时间：
2020-06-30
期刊：
影响因子：
5.2
通讯作者：
Huang，Chen
中科院分区：
文献类型：
--
作者：
Wang，Wenjing;Wang，Bo;Huang，Chen
复杂的术后并发症限制了肝移植的长期临床成功。因此，早期识别生物标志物对于移植物和患者的生存至关重要。高通量血清蛋白质组学技术提供了识别诊断和预后生物标志物的机会。本研究旨在确定并发症的血清诊断生物标志物并监测有效性。使用基质辅助激光解吸/电离飞行时间质谱 (MALDI-TOF MS) 筛选 10 名肝移植前后患者、10 名急性排斥 (AR) 患者、9 名缺血型胆道病变 (ITBL) 患者和 10 名健康对照者的血清样本，以探索多肽的差异。然后，我们使用 ELISA 和蛋白质印迹分析来验证这些潜在生物标志物的表达，并研究蛋白质组谱与临床参数的相关性。与健康对照相比，术前患者的 ACLY、FGA 和 APOA1 显着降低，并且这些患者在移植后恢复情况温和。在 AR 和 ITBL 患者中也观察到 ACLY 和 FGA 均下调。此外，进行了生物信息学分析，结果表明所鉴定的蛋白质参与糖脂代谢和凝血级联。总之，这些发现表明 ACLY、FGA 和 APOA1 可能是新型非侵入性早期生物标志物，用于检测并发症并预测肝移植的有效性。
Sophisticated postoperative complications limit the long-term clinical success of liver transplantation. Hence, early identification of biomarkers is essential for graft and patient survival. High-throughput serum proteomics technologies provide an opportunity to identify diagnostic and prognostic biomarkers. This study is aimed to identify serum diagnosis biomarkers for complications and monitor effectiveness. Serum samples from 10 paired pre- and post-liver transplant patients, 10 acute rejection (AR) patients, 9 ischemic-type biliary lesion (ITBL) patients, and 10 healthy controls were screened using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to explore divergence in polypeptide. Then, we used ELISA and western blot analysis to validate the expression of these potential biomarkers, and studied the correlation of proteomic profiles with clinical parameters. ACLY, FGA, and APOA1 were significantly lower in pre-operative patients compared with healthy controls, and these patients had modest recovery after transplantation. Downregulation of both, ACLY and FGA, was also observed in AR and ITBL patients. Furthermore, bioinformatics analysis was performed and the results suggested that the identified proteins were involved in glucolipid metabolism and the clotting cascade. Together, these findings suggest that ACLY, FGA, and APOA1 could be novel non-invasive and early biomarkers to detect complications and predict effectiveness of liver transplantation.