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

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 land...

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Main Authors: Heike Thiemeyer, Leila Taher, Jan Torben Schille, Eva-Maria Packeiser, Lisa K. Harder, Marion Hewicker-Trautwein, Bertram Brenig, Ekkehard Schütz, Julia Beck, Ingo Nolte, Hugo Murua Escobar
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/21/11481
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author Heike Thiemeyer
Leila Taher
Jan Torben Schille
Eva-Maria Packeiser
Lisa K. Harder
Marion Hewicker-Trautwein
Bertram Brenig
Ekkehard Schütz
Julia Beck
Ingo Nolte
Hugo Murua Escobar
author_facet Heike Thiemeyer
Leila Taher
Jan Torben Schille
Eva-Maria Packeiser
Lisa K. Harder
Marion Hewicker-Trautwein
Bertram Brenig
Ekkehard Schütz
Julia Beck
Ingo Nolte
Hugo Murua Escobar
author_sort Heike Thiemeyer
collection DOAJ
description 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.
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spelling doaj.art-1d53b455aeab4aa2a873fbb0640d6ac92023-11-22T20:53:18ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211148110.3390/ijms222111481An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate GenesHeike Thiemeyer0Leila Taher1Jan Torben Schille2Eva-Maria Packeiser3Lisa K. Harder4Marion Hewicker-Trautwein5Bertram Brenig6Ekkehard Schütz7Julia Beck8Ingo Nolte9Hugo Murua Escobar10Small Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, GermanyInstitute of Biomedical Informatics, Graz University of Technology, 8010 Graz, AustriaSmall Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, GermanySmall Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, GermanySmall Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, GermanyInstitute of Pathology, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, GermanyInstitute of Veterinary Medicine, University of Göttingen, 37077 Göttingen, GermanyChronix Biomedical GmbH, 37079 Göttingen, GermanyChronix Biomedical GmbH, 37079 Göttingen, GermanySmall Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, GermanySmall Animal Clinic, University of Veterinary Medicine Hannover, Foundation, 30559 Hannover, GermanyProstate 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.https://www.mdpi.com/1422-0067/22/21/11481canine prostate cancerRNA-Sequencingwhole transcriptome analysiscandidate biomarker genesanimal modelmolecular diagnostics
spellingShingle Heike Thiemeyer
Leila Taher
Jan Torben Schille
Eva-Maria Packeiser
Lisa K. Harder
Marion Hewicker-Trautwein
Bertram Brenig
Ekkehard Schütz
Julia Beck
Ingo Nolte
Hugo Murua Escobar
An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes
International Journal of Molecular Sciences
canine prostate cancer
RNA-Sequencing
whole transcriptome analysis
candidate biomarker genes
animal model
molecular diagnostics
title An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes
title_full An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes
title_fullStr An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes
title_full_unstemmed An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes
title_short An RNA-Seq-Based Framework for Characterizing Canine Prostate Cancer and Prioritizing Clinically Relevant Biomarker Candidate Genes
title_sort rna seq based framework for characterizing canine prostate cancer and prioritizing clinically relevant biomarker candidate genes
topic canine prostate cancer
RNA-Sequencing
whole transcriptome analysis
candidate biomarker genes
animal model
molecular diagnostics
url https://www.mdpi.com/1422-0067/22/21/11481
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