Plasma proteomic profiling in dogs with pheochromocytoma

Abstract

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.