| Full text | |
| Author(s): |
Pulz, Lidia H.
[1, 2]
;
Barra, Camila N.
[1, 2]
;
Alexandre, Pamela A.
[1]
;
Huete, Greice C.
[1]
;
Cadrobbi, Karine G.
[1]
;
Nishiya, Adriana T.
[3]
;
de Freitas, Silvio Henrique
[1]
;
Fukumasu, Heidge
[1]
;
Strefezzi, Ricardo F.
[1]
Total Authors: 9
|
| Affiliation: | [1] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, Pirassununga, SP - Brazil
[2] Univ Sao Paulo, Fac Vet Med & Anim Sci FMVZ, Dept Pathol, Sao Paulo, SP - Brazil
[3] Anhembi Morumbi Univ, Vet Hosp Anhembi Morumbi, Sao Paulo, SP - Brazil
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | PLoS One; v. 14, n. 6 JUN 19 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
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. (AU) | |
| FAPESP's process: | 13/13252-8 - Characterization of apoptosis related genes in canine cutaneous mast cell tumors and its value as prognostic indicators |
| Grantee: | Ricardo de Francisco Strefezzi |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 14/02493-7 - Mammary tumors of dogs and the cancer stem cell theory: a comparative and translational approach |
| Grantee: | Heidge Fukumasu |
| Support Opportunities: | Research Grants - Young Investigators Grants |