Serum proteomic approach to identifying differentially expressed proteins in effusive feline infectious peritonitis

Abstract

Feline infectious peritonitis (FIP) is a lethal, viral-induced immune-mediated disease that remains a challenge for diagnosis and treatment in cats. Proteomic profiling, which analyzes the protein content of biological samples, offers the potential to identify novel biomarkers that could improve the diagnosis and management of FIP. This study aims to assess the serum proteome and identify proteins that differentiate healthy cats from cats diagnosed with effusive FIP using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). A total of 30 cats diagnosed with effusive FIP and 27 clinically normal cats were enrolled. Twenty-three proteins were significantly (p < 0.01, ≥ fivefold change in abundance) differentially expressed between cats with effusive FIP and controls. Among these, the P2X purinoceptor, DNA topoisomerase, Notch receptor 2, and cadherin-17 were identified as key proteins of interest in cats with effusive FIP. Our findings suggest that these differentially expressed proteins could serve as potential diagnostic biomarkers and therapeutic targets for FIP. However, further studies are needed to validate these findings and explore their potential applications.

Keywords: Biomarkers; Cats; Coronavirus; Feline infectious peritonitis; Proteomics; Serum.

Fig. 1

Proteomic approach for serum analysis in effusive FIP. The proteomic workflow used to analyze serum samples from cats with effusive FIP and healthy cats for protein identification and quantification involves sample collection and preparation, protein extraction, LC–MS/MS, and bioinformatic analysis to identify and quantify differentially expressed proteins between the two groups.

Fig. 2

Representative MALDI-TOF peptide fingerprint spectra from individual serum samples. Distinct mass pattern differences were observed between FIP and non-FIP cats.

Fig. 3

The dimensional image from PCA showed the serum peptide profile distribution of all groups from MALDI-TOF spectra. The arrowheads labeled H1–H6 represent the cats in the non-FIP group, while the arrowheads labeled FIP1–FIP11 represent the cats in the FIP group.

Fig. 4

The top 10 biological processes, molecular functions, and pathways identified from the combined proteomic dataset of FIP and non-FIP cats.

Fig. 5

Differential expression analysis of the quantitative proteomics dataset. Heat map of identified serum proteins, with each column indicating a sample and each row indicating a serum protein (a). The PLSDA score plot of components one and two, comparing serum samples as they cluster (b). The dendrogram demonstrates the protein profile of each group of FIP cats with red letters and non-FIP cats with green letters (c).

Fig. 6

The volcano plot of the binary comparison of differentiated protein expression in FIP vs. non-FIP cats. The significant proteins are shown in red dots (upregulated proteins) or blue (downregulated proteins) with fold change ≥ 5 and p < 0.01. The gray dots represent no statistically significant differences in proteins.

Fig. 7

The interaction network of differentially expressed proteins in effusive FIP serum was predicted using the STITCH 5.0 software. Stronger associations are represented by thicker lines. Protein–protein interactions are shown in blue, chemical–protein interactions in green, and interactions between chemicals in red. Eight candidate upregulated proteins associated with the disease are in the red dashed circle, and downregulated proteins are in the blue dashed circle.