Research Paper Volume 12, Issue 12 pp 12119—12141
Serum proteomic predicts effectiveness and reveals potential biomarkers for complications in liver transplant patients
- 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, P R China
- 2 Department of Cell Biology and Genetics, School of Basic Medical Sciences, Xi'an Jiaotong University, Health Science Center, Shaanxi, Xi'an 710061, P R China
- 3 Department of Clinical Medicine, Medical College of Yan’an University, Yan’an 716000, P R China
- 4 Institute of Genetics and Developmental Biology, Translational Medicine Institute, Xi'an Jiaotong University, Xi'an 710061, P R China
- 5 Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong University), Ministry of Education of China, Xi'an 710061, P R China
- 6 Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, Xi'an 710004, P R China
Received: February 28, 2020 Accepted: April 20, 2020 Published: June 12, 2020
https://doi.org/10.18632/aging.103381How to Cite
Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
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.
Abbreviations
MALDI-TOF-MS: matrix-assisted laser desorption/ionization time-of-flight mass spectrometry; ELISA: enzyme-linked immunosorbent assay; ACLY: ATP citrate lyase; FGA: fibrinogen alpha chain; APOA1: apolipoprotein A1; LC-MS: liquid chromatography-mass spectrometry; AR: acute rejection; ITBL: ischemic-type biliary lesion; CHO: cholesterol; FIB: fibrinogen; ALB: albumin; ESLD: end-stage liver disease; MB-WCX: magnetic bead-based weak cation exchange; ERC: endoscopic retrograde cholangiography; ROC: receiver operating characteristic; AUC: area under the curve; WBC: white blood cell; RBC: red blood cell; PLT: platelet; NEU: neutrophil; LYM: lymphocyte; MONO: monocyte; GGT: gamma-glutamyl transferase; TBIL: total bilirubin; PT: prothrombin time; PNF: primary non-function; EAD: early allograft dysfunction; HDL: high-density lipoprotein.