Changes in Serum and Salivary Proteins in Canine Mammary Tumors.

Lorena Franco-Martínez,Vladimir Mrljak,Andrea Gelemanović,Roman Dąbrowski,Anita Horvatić,María Dolores Contreras-Aguilar,Asta Tvarijonaviciute,Silvia Martínez-Subiela,José Joaquín Cerón

doi:10.3390/ani10040741

Abstract

Simple SummaryThe present study describes for the first time the differences in the serum and saliva proteomes between healthy bitches and bitches with mammary tumors using a high-throughput proteomic approach. More than 1000 proteins were identified and 35 in serum and 49 in saliva were significantly modulated. Additionally, their related pathways were discussed in order to improve understanding of the pathophysiology of the disease and one protein, serum albumin, was further validated. The results of the present study could be a source of potential biomarkers for canine mammary tumors in saliva and serum and increase the knowledge on the pathophysiology of the disease.The aim of this study was to evaluate changes in serum and saliva proteomes in canine mammary tumors (CMT) using a high-throughput quantitative proteomic analysis in order to potentially discover possible biomarkers of this disease. Proteomes of paired serum and saliva samples from healthy controls (HC group, n = 5) and bitches with CMT (CMT group, n = 5) were analysed using a Tandem Mass Tags-based approach. Twenty-five dogs were used to validate serum albumin as a candidate biomarker in an independent sample set. The proteomic analysis quantified 379 and 730 proteins in serum and saliva, respectively. Of those, 35 proteins in serum and 49 in saliva were differentially represented. The verification of albumin in serum was in concordance with the proteomic data, showing lower levels in CMT when compared to the HC group. Some of the modulated proteins found in the present study such as haptoglobin or S100A4 have been related to CMT or human breast cancer previously, while others such as kallikrein-1 and immunoglobulin gamma-heavy chains A and D are described here for the first time. Our results indicate that saliva and serum proteomes can reflect physiopathological changes that occur in CMT in dogs and can be a potential source of biomarkers of the disease.

Highlights

Mammary tumors are the most common cancer in intact female dogs, accounting for almost 50%of all tumors [1]
The current study aims to explore for the first time changes in paired serum and saliva proteomes in bitches with mammary tumors compared to healthy ones by using Tandem Mass Tag (TMT) label-based gel-free proteomic approach
The 35 proteins differentially expressed in serum in canine mammary tumors (CMT) and HC were used for subsequent bioinformatics analysis in terms of functional clusters, according to the Protein Analysis Through Evolutionary Relationships (PANTHER)

Summary

Introduction

Mammary tumors are the most common cancer in intact female dogs, accounting for almost 50%of all tumors [1]. Animals 2020, 10, 741 by histological examination, leading to death due to distant metastases in many cases [2]. Several conditions such as hormonal imbalance, viruses, obesity, diet, genetic components, and oxidative stress contribute to CMT [1,3], the pathogenesis has not been fully elucidated to date. It is known that many biological characteristics of mammary tumors are shared between humans and dogs such as histopathologic features, biological behaviour, metastatic pattern, antigenic phenotype and expression patterns of proliferating cell nuclear antigen, cytokeratins, and calponin [4]. Dogs have been proposed as an ideal model for the investigation of human breast cancer [5]. Since humans and dogs share the same environment and are exposed to the same cancerogenic factors, spontaneously occurring malignancies in dogs have been considered as a valuable experimental model for investigation of human neoplasias [6]

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