Proteomic profiling of FFPE liver specimens of biliary atresia patients

Biliary atresia (BA) is a progressive, obstructive bile duct disease with neonatal onset and represents the leading cause of pediatric liver transplantation. The pathogenesis of BA is poorly understood and effective medical treatments are lacking.

Here, we characterized routine diagnostic formalin-fixed, paraffin-embedded (FFPE) liver specimens from BA patients (n=14) using liquid chromatography-tandem mass spectrometry (LC-MS/MS), comparing them to control liver tissue samples with no overt histopathological changes (n=7).

We identified over 5,000 proteins (protein groups), with more than 250 differentially abundant proteins (DAPs) based on log2 FC±1 and q-value<0.05 thresholds. Network and enrichment analyses (STRING database) of increased DAPs revealed terms and pathways related to “actin filament organization” (GO), “extracellular space” (GO), “lysosome” (KEGG), “neutrophil degranulation,” “innate immune system” (Reactome Pathways), and “degradation pathway of sphingolipids” (WikiPathways), among others. Decreased DAPs were associated with enrichment terms, such as “alpha-amino acid metabolic process” (GO), “mitochondrial matrix” (GO), and “tyrosine metabolism” (KEGG).

Our data so far suggest that FFPE-LC-MS/MS may provide deeper insights into the molecular alterations in BA. We are currently expanding our analyses to other neonatal cholestatic liver diseases (e.g. PFIC) to identify disease-specific proteomic signatures. These may help to improve tissue-based diagnostics and enhance our understanding of the respective disease mechanisms, potentially leading to better therapeutic options.

Publication History

Article published online:
20 January 2025