A Comparative Species Framework to Identify Candidate Salivary miRNAs Associated with Breast Cancer Risk

Area of Science:

• Comparative oncology
• Biomarker discovery
• Molecular diagnostics

Background:

• Accurate early breast cancer (BC) detection is crucial for improving patient outcomes.
• Circulating microRNAs (c-miRNAs) are emerging as potential biomarkers for cancer risk and detection.
• A comparative species approach can supplement human data for studying rare diseases like BC.

Purpose of the Study:

• To investigate whether c-miRNA expression profiles can identify individuals with early-stage BC.
• To explore the utility of a multi-species framework for identifying BC biomarkers.
• To analyze c-miRNA profiles in saliva, serum, plasma, and MDECs from humans, canines, and equines.

Main Methods:

• Collected biofluid samples (saliva, serum, plasma) from early-stage BC patients and controls.
• Analyzed mammosphere-derived epithelial cells (MDECs) from dogs (high mammary cancer incidence) and horses (low incidence).
• Utilized a comparative species approach to identify candidate c-miRNA biomarkers.

Main Results:

• Identified 16 candidate c-miRNAs upregulated in saliva of early-stage BC patients compared to controls.
• Six specific c-miRNAs (miR-361, miR-148b, miR-205, miR-186, miR-223, miR-197) were elevated in canine MDECs versus equine MDECs.
• These six c-miRNAs did not confirm early BC detection in a larger human cohort.

Conclusions:

• The study introduces a novel comparative framework for identifying human disease biomarkers by leveraging interspecies variations in cancer susceptibility.
• While specific c-miRNAs did not validate as early BC biomarkers in this pilot study, the approach offers a new avenue for biomarker discovery.
• Further research is needed to refine the comparative species approach for identifying reliable BC biomarkers.