Background: Splenic hemangiosarcoma (sHSA) is a highly aggressive cancer of endothelial cells. Due to its invasive nature, metastatic potential, and advanced stage at diagnosis, prognosis for affected dogs is poor, despite surgical resection and chemotherapy. Although histologic evaluation aids in diagnosis, grading systems often do not reflect tumor behavior, highlighting the urgency for accurate prognostic markers for sHSA. Hypothesis/
Objectives: We hypothesize that microRNA-based biomarkers can assist in the prognostication of sHSA in dogs. Animals: Archived tissue samples from 17 dogs diagnosed with sHSA were grouped based on overall survival (OS): group 1 (G1) < 90 days (N=6), group 2 (G2) 90 to 180 days (N=6), and group 3 (G3) > 180 days (N=5).
Methods: Total RNA was extracted from formalin-fixed, paraffin-embedded splenic samples and subjected to small RNA sequencing. Differentially expressed microRNAs identified in sequencing analysis were validated by qPCR.
Results: Sequencing revealed seven microRNAs differentially expressed across the groups: miR-9-5p, miR-155, miR-184, miR-335, miR-483, miR-542, and miR-8865. MiR-184 was excluded from the further analysis due to inconsistent amplification by qPCR. In addition, miR-9-5p, miR-155, miR-335, miR-483, miR-542, and miR-8865 showed no significant differences (p>0.05) by qPCR, while miR-503 was downregulated in dogs with longer OS (p=0.0147). Conclusions and Clinical Importance: miRNomics suggests potential prognostic markers based on OS. The qPCR-confirmed downregulation of miR-503 was associated with longer survival times, indicating a potential role in sHSA progression. Ongoing studies aim to expand the sample size and explore these miRNAs in liquid biopsy samples to develop non-invasive prognostic markers of sHSA.
