Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma.
Animals
Breast Neoplasms
/ genetics
Dogs
Female
Formaldehyde
Gene Expression Regulation, Neoplastic
High-Throughput Nucleotide Sequencing
Humans
Laser Capture Microdissection
Mammary Neoplasms, Animal
/ genetics
Paraffin Embedding
Prognosis
Sequence Analysis, RNA
Stromal Cells
/ metabolism
Tissue Fixation
Transcriptome
/ genetics
Breast cancer
Canine mammary carcinoma
Formalin-fixed paraffin embedded
Laser-capture microdissection
RNAseq
Tumour stroma
Journal
Disease models & mechanisms
ISSN: 1754-8411
Titre abrégé: Dis Model Mech
Pays: England
ID NLM: 101483332
Informations de publication
Date de publication:
08 08 2019
08 08 2019
Historique:
received:
06
05
2019
accepted:
09
07
2019
pubmed:
17
7
2019
medline:
9
4
2020
entrez:
17
7
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31308057
pii: dmm.040444
doi: 10.1242/dmm.040444
pmc: PMC6737962
pii:
doi:
Substances chimiques
Formaldehyde
1HG84L3525
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2019. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
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