Dados do Resumo

Título

Identification of new diagnostic and predictive targets for canine prostatic adenocarcinoma

Introdução

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 in relation to 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.

Objetivo

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.

Métodos

Sixteen animals were allocated to this study, corresponding to 4 animals in the control group and 12 animals in the neoplasia group. The extraction of samples was approved by the CEUA with Protocol 0421/2023. The first analysis carried out was the extraction of proteomic data and, subsequently, an analysis of gene expression using the integrated RTq-PCR and transcriptome techniques to identify interactions between groups. Subsequently, data cross-validation was performed with independent data obtained from canine and human prostate carcinoma databases. To identify proteins and genes differentially expressed between the experimental groups, biological triplicates were used. The results were compared using the Student's t test. Differences ​​were considered significant at p<0.05 and with expression criteria of >1.5 times logFC.

Resultados

A total of 44 proteins were detected in the analyzes performed. Among them, Vimentin and Peptidase S1 were significantly increased in the neoplasia relative to the control group. Complementary RNAseq analysis revealed that the PDGFRA, SPINT1, EFGR, CREB5, NRAS, and CTNNB1 genes were differentially expressed relative to the control group and were also enriched in pathways related to prostate cancer.

Conclusões

A possible increase in the secretion of Vimentin and Peptidase S1 proteins was identified in the neoplasia group when compared to the control group, signaling possible tumor biomarkers, as well as the PDGFRA, SPINT1, EFGR, CREB5, NRAS and CTNNB1 genes. Both proteins and genes have a positive relationship with tumor progression and development in both species. This study led to a new perspective of good biomarkers to bring greater efficiency and speed in the classification of neoplasms, as well as new targets for targeted therapy.

Financiador do resumo

CAPES, FAPESP

Palavras Chave

Prostate cancer; Transciptoma; Targeted Molecular Therapy