Identification of Potential Plasma Protein Biomarkers for Feline Pancreatic Carcinoma by Liquid Chromatography Tandem Mass Spectrometry

Abstract

In both humans and cats, pancreatic carcinoma is an aggressive cancer with a grave prognosis. Proteomics techniques have successfully identified several blood-based biomarkers of human pancreatic neoplasia. Thus, this study aims to investigate whether similar biomarkers can be identified in the plasma of cats with FePAC by using liquid chromatography tandem mass spectrometry (LC-MS/MS). To facilitate evaluation of the low abundance plasma proteome, a human-based immunodepletion device (MARS-2) was first validated for use with feline plasma. Marked reduction and/or complete removal of albumin and immunoglobulins was confirmed by analysis of electrophoretograms and mass spectral data. Subsequently, plasma collected from 9 cats with pancreatic carcinoma (FePAC), 10 cats with symptomatic pancreatitis, and 10 healthy control cats was immunodepleted and subjected to LC-MS/MS. Thirty-seven plasma proteins were found to be differentially expressed (p<0.05 in one-way ANOVA, FC>2 in fold change analysis). Among these proteins, ETS variant transcription factor 4 (p<0.05) was overexpressed, while gelsolin (p<0.01), tryptophan 2,3-dioxygenase (p<0.05), serpin family F member 1 (p<0.01), apolipoprotein A-IV (p<0.01), and phosphatidylinositol-glycan-specific phospholipase D (p<0.05) were down-regulated in cats with FePAC. Further studies on these potential biomarkers are needed to investigate their diagnostic value.