Abstract 5693: Diagnostic and predictive biomarkers for canine prostatic carcinoma: translational therapeutic insights

The prostate is an organ prone to diseases typical of human aging, with benign and malignant prostatic disorders being among the most common diseases that affect men. There are a wide variety of treatment options for diagnosing prostate cancer in humans, depending on the risk category the disease falls into. The dog is the only mammal, besides man, that spontaneously develops canine prostatic hyperplasia (PH), prostatic atrophy and prostatic carcinoma (PCa), which are associated with age and androgenic hormones. However, unlike PCa in humans, PCa in dogs is not androgen dependent, therefore androgen deprivation therapy is not effective, and animals develop castration-resistant prostatic carcinoma (CRPC). Many treatment modalities usually for human PCa cannot be applied in CRPC. And regarding dogs, unfortunately, there is still no effective therapy for the treatment of these tumors. Available pharmacological treatments are scarce, based primarily on the prescription of anti-inflammatory drugs, with a low degree of survival. Therefore, we intend to carry out new translational studies on human and canine PCa samples, aiming to identify predictive markers and potential common therapeutic targets, to subsequently elucidate the antitumor effect of existing drugs, aiming to develop targeted therapies. The study included 20 animals, with 4 in the control group and 16 in the neoplasia group, under CEUA approval. Samples underwent proteomic analysis, RT-qPCR, RNA sequencing (RNAseq), and Next-Generation Sequencing (NGS) to evaluate gene expression patterns, tumor microenvironment interactions, and immune cell infiltrate estimates. Cross-validation with independent data from canine and human prostate carcinoma databases was performed. Biological triplicates were analyzed, and differential protein and gene expression were assessed using Student’s t-test (p < 0.05, expression change > 1.5x). A total of 44 proteins, including significantly elevated levels of Vimentin and Peptidase S1, were identified in the neoplasia group. Additionally, 1,412 differentially expressed genes were enriched in prostate cancer-related pathways, with 536,200 SNPs identified across 291 genes in the canine exome. Thirteen genes co-expressed in RNAseq and NGS analyses emerged as potential direct therapy targets. Increased secretion of Vimentin and Peptidase S1 in the neoplasia group highlighted their potential as tumor biomarkers. These findings reveal a significant overlap in tumor progression and biomarker expression between canine and human PCa, offering promising avenues for translational studies to develop effective diagnostic tools and targeted therapies for both species. Citation Format: Alexandre Matheus Baesso Cavalca, Marxa Leao Figueiredo, Maricy Apparício Ferreira, Carlos Eduardo Fonseca Alves. Diagnostic and predictive biomarkers for canine prostatic carcinoma: translational therapeutic insights [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5693.