A Comparative Meta-Analysis and in silico Analysis of Differentially Expressed Genes and Proteins in Canine and Human Bladder Cancer

Abstract

Canine and human bladder cancer present similar anatomical, morphological, and molecular characteristics, and dogs can be considered a model for human bladder cancer. However, the veterinary literature lacks information regarding cross-validation analysis between human and canine large-scale data. Therefore, this research aimed to perform a meta-analysis of the canine literature on bladder cancer, identifying genes and proteins previously evaluated in these studies. In addition, we also performed a cross-validation of the canine transcriptome data and the human data from The Cancer Genome Atlas (TCGA) to identify potential markers for both species. The meta-analysis was performed using the following indexing terms: “bladder” AND “carcinoma” AND “dog” in different international databases, and 385 manuscripts were identified in our initial search. Then, several inclusion criteria were applied, and only 25 studies met these criteria. Among these studies, five presented transcriptome data, and 20 evaluated only isolated genes or proteins. Regarding the studies involving isolated protein analysis, the HER-2 protein was the most studied (3/20), followed by TAG-72 (2/20), COX-2 (2/20), survivin (2/20), and CK7 (2/20), and the remaining nine studies evaluated one isolated protein each. Regarding the cross-validation analysis of human and canine transcriptome data, we identified 35 dysregulated genes, including ERBB2, TP53, EGFR , and E2F2 . Our results demonstrate that the canine literature on bladder cancer previously focused on the evaluation of isolated markers with no association with patient survival. This limitation may be related to the lack of a homogenous protocol for treating patients and the lack of follow-up during treatment. In addition, the lack of information regarding tumor muscle invasion can be considered an important limitation when comparing human and canine bladder tumors. Our in silico analysis involving canine and human transcriptome data provided several genes with the potential to be markers for both human and canine bladder tumors, and these genes should be considered for future studies on canine bladder cancer.

Molecular Markers in Urinary Bladder Cancer: Applications for Diagnosis, Prognosis and Therapy

“…GATA-Binding Protein 3 (GATA3) is a zinc finger transcription factor that has been used in human medicine as a diagnostic and prognostic marker of urothelial carcinoma [ 117 , 118 , 119 ]. In a review article, Knapp et al, 2014 [ 114 ] showed the expression of GATA3 in a canine TCC bladder tissue sample.…”

Grading Systems for Canine Urothelial Carcinoma of the Bladder: A Comparative Overview

“…Valli et al also described the way a carcinoma spreads into the wall of the bladder, which can be tentacular when the tumor infiltrates the strands, nests, and individual cells, inserting itself between normal bladder structures, or it can present a “broad front”, when the tumor advances uniformly though the bladder tissue [ 12 ]. Canine BUCs can invade adjacent tissues and organs, such as the ureter, prostatic urethra, and prostate gland, and moreover, the tumor can spread by means of vascular and lymphatic vessels [ 12 , 21 , 22 ]. Lymphatic invasion has recently been proven to be a significant negative prognostic factor [ 10 ].…”

“…Moreover, the lack of follow-up studies demonstrating the association between the grading systems and clinical outcomes discourages clinicians from performing a biopsy for tumor classification. In clinical routines, catheter-based cytology and molecular diagnosis (evaluation of BRAF mutation) have been used for final diagnosis, and in advanced tumors, biopsy is not usually performed for the application of grading systems [ 22 ].…”

“…In addition, research studies have also demonstrated that vascular invasion correlates with a worse outcome in human patients [ 40 ], and lymphatic invasion was also recently associated with a worse prognosis in canine BUCs [ 22 ]. Lymphovascular (LVI) invasion is recognized as a marker of tumor malignancy, suggesting aggressive biological behavior and increased probability of metastatic disease.…”

A Comparative in Silico Analysis of CD24’s Prognostic Value in Human and Canine Prostate Cancer

“…The systematic review was performed according to Gambini et al [19]. Briefly, the initial search was performed on the PubMed, MEDLINE, and Scielo databases using the following indexing terms "CD24" AND "prostate" AND "cancer" with no restrictions regarding the year of publication.…”