Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma
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...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2019-08-01
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| Series: | Disease Models & Mechanisms |
| Subjects: | |
| Online Access: | http://dmm.biologists.org/content/12/8/dmm040444 |
| _version_ | 1819078529211432960 |
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| author | Parisa Amini Sina Nassiri Julia Ettlin Alexandra Malbon Enni Markkanen |
| author_facet | Parisa Amini Sina Nassiri Julia Ettlin Alexandra Malbon Enni Markkanen |
| author_sort | Parisa Amini |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T19:14:32Z |
| format | Article |
| id | doaj.art-762cea75dc0b487bac2cff7781f45c2b |
| institution | Directory Open Access Journal |
| issn | 1754-8403 1754-8411 |
| language | English |
| last_indexed | 2024-12-21T19:14:32Z |
| publishDate | 2019-08-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Disease Models & Mechanisms |
| spelling | doaj.art-762cea75dc0b487bac2cff7781f45c2b2022-12-21T18:53:06ZengThe Company of BiologistsDisease Models & Mechanisms1754-84031754-84112019-08-0112810.1242/dmm.040444040444Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinomaParisa Amini0Sina Nassiri1Julia Ettlin2Alexandra Malbon3Enni Markkanen4 Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland Bioinformatics Core Facility, Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland Institute of Veterinary Pathology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland Institute of Veterinary Pharmacology and Toxicology, Vetsuisse Faculty, University of Zürich, CH-8057 Zürich, Switzerland 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.http://dmm.biologists.org/content/12/8/dmm040444Formalin-fixed paraffin embeddedRNAseqLaser-capture microdissectionCanine mammary carcinomaBreast cancerTumour stroma |
| spellingShingle | Parisa Amini Sina Nassiri Julia Ettlin Alexandra Malbon Enni Markkanen Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma Disease Models & Mechanisms Formalin-fixed paraffin embedded RNAseq Laser-capture microdissection Canine mammary carcinoma Breast cancer Tumour stroma |
| title | Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma |
| title_full | Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma |
| title_fullStr | Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma |
| title_full_unstemmed | Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma |
| title_short | Next-generation RNA sequencing of FFPE subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma |
| title_sort | next generation rna sequencing of ffpe subsections reveals highly conserved stromal reprogramming between canine and human mammary carcinoma |
| topic | Formalin-fixed paraffin embedded RNAseq Laser-capture microdissection Canine mammary carcinoma Breast cancer Tumour stroma |
| url | http://dmm.biologists.org/content/12/8/dmm040444 |
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