MicroRNA Expression Changes and Integrated Pathways Associated With Poor Outcome in Canine Osteosarcoma

Area of Science:

• Veterinary Oncology
• Molecular Biology
• Biomarker Discovery

Background:

• Osteosarcoma (OS) is an aggressive bone cancer in dogs with poor metastatic prognosis.
• Current prognostic markers for canine OS are limited.
• MicroRNAs (miRNAs) are small non-coding RNAs involved in gene regulation and are potential biomarkers due to their stability.

Purpose of the Study:

• To identify miRNA expression profiles in canine OS tumors and serum that can predict patient prognosis.
• To develop predictive models for distinguishing between good and poor outcomes in canine OS patients.
• To explore miRNA-mRNA interactions disrupted in canine OS and their contribution to metastasis.

Main Methods:

• RT-qPCR was used to measure the expression of 190 miRNAs in canine OS tumors and serum.
• Differential expression analysis was performed on a subset of samples to select candidate miRNAs.
• Cox proportional hazards regression and Kaplan-Meier analysis were used to develop and validate prognostic models.
• Integrated analysis of miRNA and gene expression data was conducted.

Main Results:

• A three-miRNA tumor-based model and a two-miRNA serum-based model were developed.
• Both models demonstrated the ability to distinguish between good and poor prognosis in canine OS patients.
• Integrated analysis suggested that disrupted miRNA-mRNA interactions in the tumor microenvironment contribute to the metastatic phenotype.

Conclusions:

• miRNA expression profiles in tumors and serum can serve as reliable prognostic biomarkers for canine osteosarcoma.
• The identified miRNA models offer potential tools for improving patient management and treatment strategies.
• Further investigation into miRNA-mRNA interactions may reveal novel therapeutic targets for aggressive canine OS.