SFRP1 Expression is Inversely Associated With Metastasis Formation in Canine Mammary Tumours.
J Mammary Gland Biol Neoplasia
; 28(1): 15, 2023 07 04.
Article
en En
| MEDLINE
| ID: mdl-37402051
ABSTRACT
BACKGROUND:
Canine mammary tumours (CMTs) are the most frequent tumours in intact female dogs and show strong similarities with human breast cancer. In contrast to the human disease there are no standardised diagnostic or prognostic biomarkers available to guide treatment. We recently identified a prognostic 18-gene RNA signature that could stratify human breast cancer patients into groups with significantly different risk of distant metastasis formation. Here, we assessed whether expression patterns of these RNAs were also associated with canine tumour progression.METHOD:
A sequential forward feature selection process was performed on a previously published microarray dataset of 27 CMTs with and without lymph node (LN) metastases to identify RNAs with significantly differential expression to identify prognostic genes within the 18-gene signature. Using an independent set of 33 newly identified archival CMTs, we compared expression of the identified prognostic subset on RNA and protein basis using RT-qPCR and immunohistochemistry on FFPE-tissue sections.RESULTS:
While the 18-gene signature as a whole did not have any prognostic power, a subset of three RNAs Col13a1, Spock2, and Sfrp1, together completely separated CMTs with and without LN metastasis in the microarray set. However, in the new independent set assessed by RT-qPCR, only the Wnt-antagonist Sfrp1 showed significantly increased mRNA abundance in CMTs without LN metastases on its own (p = 0.013) in logistic regression analysis. This correlated with stronger SFRP1 protein staining intensity of the myoepithelium and/or stroma (p < 0.001). SFRP1 staining, as well as ß-catenin membrane staining, was significantly associated with negative LN status (p = 0.010 and 0.014 respectively). However, SFRP1 did not correlate with ß-catenin membrane staining (p = 0.14).CONCLUSION:
The study identified SFRP1 as a potential biomarker for metastasis formation in CMTs, but lack of SFRP1 was not associated with reduced membrane-localisation of ß-catenin in CMTs.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Neoplasias Mamarias Animales
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
J Mammary Gland Biol Neoplasia
Asunto de la revista:
NEOPLASIAS
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania