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. 2021 Jul 26:12:672829.
doi: 10.3389/fimmu.2021.672829. eCollection 2021.

Proteomics in Liver Transplantation: A Systematic Review

Victor López-López  1   2 , Fernando Pérez-Sánz  3 , Carlos de Torre-Minguela  2 , Josefa Marco-Abenza  4 , Ricardo Robles-Campos  1   2 , Francisco Sánchez-Bueno  1   2 , José A Pons  2   5 , Pablo Ramírez  1   2 , Alberto Baroja-Mazo  2
Affiliations

Proteomics in Liver Transplantation: A Systematic Review

Victor López-López et al. Front Immunol. .

Abstract

Background: Although proteomics has been employed in the study of several models of liver injury, proteomic methods have only recently been applied not only to biomarker discovery and validation but also to improve understanding of the molecular mechanisms involved in transplantation.

Methods: The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology and the guidelines for performing systematic literature reviews in bioinformatics (BiSLR). The PubMed, ScienceDirect, and Scopus databases were searched for publications through April 2020. Proteomics studies designed to understand liver transplant outcomes, including ischemia-reperfusion injury (IRI), rejection, or operational tolerance in human or rat samples that applied methodologies for differential expression analysis were considered.

Results: The analysis included 22 studies after application of the inclusion and exclusion criteria. Among the 497 proteins annotated, 68 were shared between species and 10 were shared between sample sources. Among the types of studies analyzed, IRI and rejection shared a higher number of proteins. The most enriched pathway for liver biopsy samples, IRI, and rejection was metabolism, compared to cytokine-cytokine receptor interactions for tolerance.

Conclusions: Proteomics is a promising technique to detect large numbers of proteins. However, our study shows that several technical issues such as the identification of proteoforms or the dynamic range of protein concentration in clinical samples hinder the successful identification of biomarkers in liver transplantation. In addition, there is a need to minimize the experimental variability between studies, increase the sample size and remove high-abundance plasma proteins.

Keywords: PRISMA; ischemia – reperfusion; mass spectrometry; rejection; tolerance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram through the different phases of studies selection for systematic review.
Figure 2
Figure 2
Candidate protein biomarkers from different sample source. (A–D) Venn diagram among all selected studies in a cross-species (A–C) or cross-sample source (D) analysis. (E, F) Bar graph representing the most shared proteins among all selected studies in serum/plasma (E) or liver biopsies (F).
Figure 3
Figure 3
Candidate protein biomarkers from different types of study. (A–C) Bar graph representing the most shared proteins among all selected studies in IRI (A), rejection (B) or tolerance (C). (D) Venn diagram among all selected publications in cross-type of study analysis.
Figure 4
Figure 4
Differential pattern of protein expression. (A) Comparison of differential expression patterns observed for proteins among all selected studies expressed as a Venn diagram. (B) Heat plot of the list of proteins that had evidence supporting both types of expression changes.
See this image and copyright information in PMC

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