# Quantitative proteomics of formalin-fixed, paraffin-embedded cardiac specimens uncovers protein signatures of specialized regions and patient groups

## TL;DR

This study shows that archived heart tissue can be used for detailed protein analysis, revealing disease markers and specialized regions in the heart.

## Contribution

The study establishes FFPE heart tissue as a viable and robust resource for high-resolution cardiac proteomics.

## Key findings

- FFPE heart tissue preserves proteomic profiles suitable for high-resolution, quantitative analysis.
- Distinct protein signatures were identified in the sinoatrial node and in arrhythmogenic cardiomyopathy biopsies.
- The method enables retrospective molecular profiling of archived cardiac specimens at scale.

## Abstract

Proteomic technologies have advanced our understanding of disease mechanisms, patient stratification and targeted therapies. However, applying cardiac proteomics in translational research requires overcoming the barrier of tissue accessibility. Formalin-fixed, paraffin-embedded (FFPE) heart tissue, widely preserved in pathology collections, remains a largely untapped resource. Here we demonstrate that proteomic profiles are well preserved in FFPE human heart specimens and compatible with high-resolution, quantitative analysis. Quantifying approximately 4,000 proteins per sample, we show this approach effectively distinguishes disease states and subanatomical regions, revealing distinct underlying protein signatures. Specifically, the human sinoatrial node exhibited enrichment of collagen VI and G protein-coupled receptor signaling. Myocardial biopsies from patients with arrhythmogenic cardiomyopathy were characterized by fibrosis and metabolic/cytoskeletal derangements, clearly separating them from donor heart biopsies. This study establishes FFPE heart tissue as a robust resource for cardiac proteomics, enabling retrospective molecular profiling at scale and unlocking archived specimens for disease discovery and precision cardiology.

Achter et al. established a protocol for quantitative proteomic profiling of formalin-fixed, paraffin-embedded human cardiac tissues, benchmarked against fresh-frozen samples. They applied it to stratify patients with arrhythmogenic cardiomyopathy and performed deep proteomic analysis of the human sinoatrial node.