Affordable Access

deepdyve-link
Publisher Website

Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma.

Authors
  • Amini, Parisa1
  • Nassiri, Sina2
  • Ettlin, Julia1
  • Malbon, Alexandra3
  • Markkanen, Enni4
  • 1 Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland. , (Switzerland)
  • 2 Bioinformatics Core Facility, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland. , (Switzerland)
  • 3 Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland. , (Switzerland)
  • 4 Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland [email protected] , (Switzerland)
Type
Published Article
Journal
Disease Models & Mechanisms
Publisher
The Company of Biologists
Publication Date
Aug 08, 2019
Volume
12
Issue
8
Identifiers
DOI: 10.1242/dmm.040444
PMID: 31308057
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Spontaneous canine simple mammary carcinomas (mCA) are often viewed as models of human mCA. Cancer-associated stroma (CAS) is central for initiation and progression of human cancer, and is likely to play a key role in canine tumours as well. However, canine CAS lacks characterisation and it remains unclear how canine and human CAS compare. Formalin-fixed paraffin embedded (FFPE) tissue constitutes a valuable resource of patient material, but chemical crosslinking has largely precluded its analysis by next-generation RNA sequencing (RNAseq). We have recently established a protocol to isolate CAS and normal stroma from archival FFPE tumours using laser-capture microdissection followed by RNAseq. Using this approach, we have analysed stroma from 15 canine mCA. Our data reveal strong reprogramming of canine CAS. We demonstrate a high-grade molecular homology between canine and human CAS, and show that enrichment of upregulated canine CAS genes strongly correlates with the enrichment of an independently derived human stromal signature in the TCGA breast tumour dataset. Relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Finally, we establish the prognostic potential of the canine CAS signature in human samples, emphasising the relevance of studying canine CAS as a model of the human disease. In conclusion, we provide a proof-of-principle to analyse specific subsections of FFPE tissue by RNAseq, and compare stromal gene expression between human and canine mCA to reveal molecular drivers in CAS supporting tumour growth and malignancy. © 2019. Published by The Company of Biologists Ltd.

Report this publication

Statistics

Seen <100 times