SFRP1 Expression is Inversely Associated With Metastasis Formation in Canine Mammary Tumours

Area of Science:

• Veterinary oncology
• Molecular biology
• Biomarker discovery

Background:

• Canine mammary tumours (CMTs) are common in intact female dogs and resemble human breast cancer.
• Unlike human breast cancer, CMTs lack standardized diagnostic and prognostic biomarkers.
• A previously identified 18-gene RNA signature for human breast cancer metastasis risk was investigated for its relevance in CMTs.

Purpose of the Study:

• To evaluate the prognostic power of a human breast cancer-derived 18-gene RNA signature in canine mammary tumours.
• To identify specific RNA biomarkers within the signature associated with lymph node metastasis in CMTs.
• To validate the expression and potential role of identified biomarkers in canine tumour progression.

Main Methods:

• A microarray dataset of 27 CMTs was analyzed using feature selection to identify differentially expressed RNAs.
• An independent set of 33 CMTs was used for validation via RT-qPCR (RNA) and immunohistochemistry (protein).
• Expression levels of selected RNAs and proteins were correlated with lymph node metastasis status.

Main Results:

• The 18-gene signature did not prognosticate CMT metastasis.
• A three-gene subset (Col13a1, Spock2, Sfrp1) distinguished between metastatic and non-metastatic CMTs in the initial set.
• SFRP1 mRNA and protein were significantly higher in CMTs without lymph node metastasis, correlating with negative lymph node status.

Conclusions:

• SFRP1 is a potential biomarker for predicting metastasis in canine mammary tumours.
• SFRP1 expression is associated with reduced metastasis in CMTs.
• SFRP1's role in Wnt signaling pathway and β-catenin localization in CMTs requires further investigation.