Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: In liver transplantation, much of factors have a pernicious influence on liver donor quality, such as hepatic steatosis, long term of donor hypotension, cardiac arrest time, warm ischemia time, cold ischemia time, et al. The molecular basis of different liver donor with distinct susceptibility to ischemia reperfusion injury (IRI) remains undefined. Using isobaric tags for relative and absolute quantification (iTRAQ), we investigated the proteomic alterations in different quality of liver graft in liver transplantation.
*Methods: 15 transplanted liver donor samples were collected and divided into three groups: optimal graft function (OG), early allograft dysfunction (EAD), primary nonfunction (PNF) group. Each pair biopsy was taken before anhepatic phase and at the end of transplantation. 5 liver samples were obtained at the start of the retrieval operation, which was set up as normal control group. Comparative quantitative proteomics was performed. Label-free LC−MRM-MS-based targeted method was further employed for verification. For further investigation of liver-type fatty acid-binding protein (L-FABP) protein expression, human liver samples and serum were collected for analysis, and moue IRI model was also adopted for L-FABP detection.
*Results: A total of 6505 proteins were preliminarily identified in the human liver donor. As for the comparison of IRI related proteins, 318 proteins were identified to be expressed differentially compared to normal control group. 22 proteins play a central role in the IRI injury process. However, a higher uniformity was noted in the PNF group. More than 160 differentially expressed proteins were detected in PNF group, compared to 54 and 36 proteins in the EAD and OGF groups respectively. Through MRM verification, 15 proteins were verified to be related to IRI injury, including decreased expression of CNDP2, PRDX1, HGD, L-FABP, THIO, 6PGD, HPPD in PNF group. In muse IRI model, serum L-FABP and its tissue expression were corresponding to the ALT variation curve, meaning an effective injury biomarker of liver injury. Serum L-FABP in both donor and reperfusion phase was higher in EAD group than OG group. And higher level of L-FABP after reperfusion was showed in EAD and PNF group than OG group implicated incompetent liver donor quality. Lower expression of L-FABP in liver tissue after cold preservation or reperfusion might have lower possibility to occur PNF after transplantation.
*Conclusions: Suboptimal donor liver is more sensible to IRI injury companied with more protein changes in biological process and molecular function. L-FABP might be an effective biomarker for evaluation donor quality and postoperative recovery in liver transplantation.
To cite this abstract in AMA style:Chen M, Zhang Y, Han M, Ju W, Zhao Q, Chen Y, Wang D, He X. Comparative Proteomics Analysis Identifies L-FABP as a Putative Biomarker of Graft Injury During Liver Transplantation Using the ITRAQ/MRM Approach [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/comparative-proteomics-analysis-identifies-l-fabp-as-a-putative-biomarker-of-graft-injury-during-liver-transplantation-using-the-itraq-mrm-approach/. Accessed March 8, 2021.
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