An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes

• Published in: International journal of molecular sciences Vol. 22; no. 21; p. 11481
• Main Authors: Thiemeyer, Heike, Taher, Leila, Schille, Jan Torben, Packeiser, Eva-Maria, Harder, Lisa K, Hewicker-Trautwein, Marion, Brenig, Bertram, Schütz, Ekkehard, Beck, Julia, Nolte, Ingo, Murua Escobar, Hugo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 25-10-2021; MDPI
• Subjects: 1-Phosphatidylinositol 3-kinase; animal model; Animals; Apoptosis; Autophagy; Biomarkers; Biomarkers, Tumor - genetics; Biopsy; candidate biomarker genes; Candidates; canine prostate cancer; Cell cycle; Cell death; Cell surface; Computational Biology - methods; Cytokines; Deregulation; Diagnostic systems; Dogs; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes; Genomes; Immune system; Inflammation; Inflammatory response; Kinases; Male; molecular diagnostics; Phagocytosis; Phase transitions; Phosphorylation; Prostate cancer; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Proteins; RNA-Seq - methods; RNA-Sequencing; Transcription; Transcriptome; whole transcriptome analysis; candidate biomarker genes; molecular diagnostics; whole transcriptome analysis; canine prostate cancer; animal model; RNA-Sequencing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111481

Prostate cancer (PCa) in dogs is a highly malignant disease akin to its human counterpart. In contrast to the situation in humans, multi-gene approaches facilitating risk stratification of canine PCa are barely established. The aims of this study were the characterization of the transcriptional landscape of canine PCa and the identification of diagnostic, prognostic and/or therapeutic biomarkers through a multi-step screening approach. RNA-Sequencing of ten malignant tissues and fine-needle aspirations (FNA), and 14 nonmalignant tissues and FNAs was performed to find differentially expressed genes (DEGs) and deregulated pathways. The 4098 observed DEGs were involved in 49 pathways. These 49 pathways could be grouped into five superpathways summarizing the hallmarks of canine PCa: (i) inflammatory response and cytokines; (ii) regulation of the immune system and cell death; (iii) cell surface and PI3K signaling; (iv) cell cycle; and (v) phagosome and autophagy. Among the highly deregulated, moderately to strongly expressed DEGs that were members of one or more superpathways, 169 DEGs were listed in relevant databases and/or the literature and included members of the PCa pathway, oncogenes, prostate-specific genes, and druggable genes. These genes are novel and promising candidate diagnostic, prognostic and/or therapeutic canine PCa biomarkers.