Blacklock, Kelly Bowlt, Birand, Zeynep, Biasoli, Deborah, Fineberg, Elena, Murphy, Sue, Flack, Debs, Bass, Joyce, Di Palma, Stefano, Blackwood, Laura, McKay, Jenny et al (show 5 more authors)
(2018)
Identification of molecular genetic contributants to canine cutaneous mast cell tumour metastasis by global gene expression analysis.
PLOS ONE, 13 (12).
e0208026-.
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Identification of molecular genetic contributants to canine cutaneous mast cell tumour metastasis by global gene expression analysis.pdf - Published version Download (1MB) | Preview |
Abstract
Cutaneous mast cell tumours are one of the most common canine cancers. Approximately 25% of the tumours metastasise. Activating c-kit mutations are present in about 20% of tumours, but metastases occur in the absence of mutations. Tumour metastasis is associated with significantly diminished survival in spite of adjuvant chemotherapy. Available prognostic tests do not reliably predict whether a tumour will metastasise. In this study we compared the global expression profiles of 20 primary cutaneous mast cell tumours that metastasised with those of 20 primary tumours that did not metastasise. The objective was to identify genes associated with mast cell tumour metastatic progression that may represent targets for therapeutic intervention and biomarkers for prediction of tumour metastasis. Canine Gene 1.1 ST Arrays were employed for genome-wide expression analysis of formalin-fixed, paraffin-embedded biopsies of mast cell tumours borne by dogs that either died due to confirmed mast cell tumour metastasis, or were still alive more than 1000 days post-surgery. Decreased gene expression in the metastasising tumours appears to be associated with a loss of cell polarity, reduced cell-cell and cell-ECM adhesion, and increased cell deformability and motility. Dysregulated gene expression may also promote extracellular matrix and base membrane degradation, suppression of cell cycle arrest and apoptosis, and angiogenesis. Down-regulation of gene expression in the metastasising tumours may be achieved at least in part by small nucleolar RNA-derived RNA and microRNA-effected gene silencing. Employing cross-validation, a linear discriminant analysis-based classifier featuring 19 genes that displayed two-fold differences in expression between metastasising and non-metastasising tumours was estimated to classify metastasising and non-metastasising tumours with accuracies of 90-100% and 70-100%, respectively. The differential expression of 9 of the discriminator genes was confirmed by quantitative reverse transcription-PCR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Mast Cells, Skin, Animals, Dogs, Skin Neoplasms, Dog Diseases, Neovascularization, Pathologic, Biopsy, Oligonucleotide Array Sequence Analysis, Discriminant Analysis, Gene Expression Profiling, Reverse Transcriptase Polymerase Chain Reaction, Down-Regulation, Gene Expression Regulation, Neoplastic, Female, Male, Mastocytoma, Skin, Transcriptome |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 May 2019 09:10 |
| Last Modified: | 19 Jan 2023 00:45 |
| DOI: | 10.1371/journal.pone.0208026 |
| Open Access URL: | https://doi.org/10.1371/journal.pone.0208026 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3041405 |
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