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

Parisa Amini, Sina Nassiri, Julia Ettlin, Alexandra Malbon, Enni Markkanen

Research output: Contribution to journalArticlepeer-review

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 highgrade 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.
Original languageEnglish
Article numberdmm040444
Pages (from-to)1-10
JournalDisease Models and Mechanisms
Volume12
DOIs
Publication statusPublished - 8 Aug 2019

Keywords

  • Formalin-fixed paraffin embedded
  • RNAseq
  • Laser-capture microdissection
  • Canine mammary carcinoma
  • Breast cancer
  • Tumour stroma

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