Plasma proteomic profiling in dogs with pheochromocytoma.

Abstract

Background: Pheochromocytomas (PCCs) in dogs are challenging to diagnose. Plasma proteomics offers a minimally invasive approach to identify circulating biomarkers and disease-relevant pathways.

Hypothesis/objectives: To compare the plasma proteome of dogs with PCC and controls to (1) identify differentially abundant proteins, (2) characterize altered pathways, and (3) nominate candidate circulating biomarkers and therapeutic targets.

Animals: Plasma from 10 client-owned PCC dogs and 10 healthy controls.

Methods: Multicenter, retrospective, observational, exploratory study using label-free liquid chromatography-mass spectrometry. Primary outcomes were the identification of differentially abundant proteins and characterization of altered pathways and protein functions.

Results: Principal component analysis demonstrated clear separation between PCC and control dogs. Of 261 reliably quantified proteins, 51 were differentially abundant (false discovery rate-adjusted P < .05). Of these, 33 had a log2 fold change of >1 or < -1, with 15 showing higher and 18 lower plasma abundance in PCC. Compared with controls, PCC dogs showed increased abundance of proteins linked to cell adhesion/migration and metastatic potential, hemostasis, and regulation of apoptotic signaling, alongside alterations in oxidative stress and metabolic processes. Several proteins with higher abundance, including CD44, peroxiredoxin-2, and peptidyl-prolyl cis-trans isomerase, emerged as promising candidates for therapeutic exploration.

Conclusions and clinical importance: Dogs with PCC exhibit a distinct circulating protein signature vs healthy controls, providing clues to PCC pathogenesis and nominating proteins as diagnostic biomarker candidates and potential therapeutic targets.