Identification of two molecular subtypes in canine mast cell tumours through gene expression profiling.

Autor: Pulz LH; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.; Department of Pathology, Faculty of Veterinary Medicine and Animal Science- FMVZ, University of Sao Paulo, São Paulo, SP, Brazil., Barra CN; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.; Department of Pathology, Faculty of Veterinary Medicine and Animal Science- FMVZ, University of Sao Paulo, São Paulo, SP, Brazil., Alexandre PA; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil., Huete GC; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil., Cadrobbi KG; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil., Nishiya AT; Veterinary Hospital Anhembi Morumbi, R. Conselheiro Lafaiete, São Paulo-SP, Anhembi Morumbi University, São Paulo, SP, Brazil., de Freitas SH; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil., Fukumasu H; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil., Strefezzi RF; Department of Veterinary Medicine, Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, SP, Brazil.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2019 Jun 19; Vol. 14 (6), pp. e0217343. Date of Electronic Publication: 2019 Jun 19 (Print Publication: 2019).
DOI: 10.1371/journal.pone.0217343
Abstrakt: Mast cell tumours (MCTs) are common neoplasms in dogs and are usually regarded as potentially malignant. Several studies have attempted to identify biomarkers to better predict biological behaviours for this tumour. The aim of this study was to identify pathways connected to clinical and histopathological malignancies, shorter survival times, and poor prognoses associated with MCTs. We performed genome-wide gene expression analyses on tissues obtained from 15 dogs with single MCTs, and identified two distinct tumour subtypes-high-risk and low-risk-associated with differences in histological grades, survival times, Ki67 indices, and occurrence of death due the disease. Comparative analyses of RNA sequence profiles revealed 71 genes that were differentially expressed between high- and low-risk MCTs. In addition to these analyses, we also examined gene co-expression networks to explore the biological functions of the identified genes. The network construction revealed 63 gene modules, of which 4 were significantly associated with the more aggressive tumour group. Two of the gene modules positively correlated with high-risk MCTs were also associated with cell proliferation and extracellular matrix-related terms. At the top of the extracellular matrix module category, genes with functions directly related to those of cancer-associated fibroblasts (CAFs) were identified. Immunohistochemical analyses also revealed a greater number of CAFs in high-risk MCTs. This study provides a method for the molecular characterisation of canine MCTs into two distinct subtypes. Our data indicate that proliferation pathways are significantly involved in malignant tumour behaviours, which are known to be relevant for the induction and maintenance of MCTs. Finally, animals presenting high-risk MCTs overexpress genes associated with the extracellular matrix that can be robustly linked to CAF functions. We suggest that CAFs in the MCT stroma contribute to cancer progression.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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