A new study from Brazil has used gene expression profiling to identify three distinct molecular subtypes of canine splenic hemangiosarcoma, each with different therapeutic implications.
The study analyzed tumor samples from 27 dogs with splenic HSA using a 48-gene qPCR panel. The goal was to move beyond traditional histopathology and identify molecular signatures that could guide more precise treatment decisions.
The researchers identified three groups:
Group 1 (8 samples) showed elevated expression of genes including MET, FLT3, AKT2, and PDGFRA, suggesting activation of the PI3K/AKT and MAPK pathways. These tumors also had low expression of genes targeted by conventional chemotherapies, indicating potential resistance to standard protocols.
Group 2 (10 samples) overexpressed genes associated with resistance to apoptosis and enhanced cell survival, including BCL2, NOTCH1, RET, and KIT. This profile suggests potential for targeted therapies like toceranib, masitinib, or venetoclax.
Group 3 (9 samples) was characterized by increased expression of MYC, TOP2A, RRM2, TYMS, and BRCA1, genes associated with high proliferative activity. These tumors had higher mitotic counts and may be more responsive to conventional agents like doxorubicin.
The study used FFPE-derived tumor RNA within a qPCR-based precision oncology framework, demonstrating that this approach is practical and cost-effective compared to NGS-based methods. The researchers note that gene expression profiling captures functional pathway activity, while DNA-based mutation panels primarily detect genomic alterations that may not indicate functional relevance.
The authors caution that this was a retrospective study with a relatively small cohort, and the proposed molecular groups have not been validated in an independent external dataset. The dogs in the study were not prospectively treated according to the cluster-based therapeutic hypotheses, and longitudinal survival outcomes were not correlated with the molecular findings. The work should be interpreted as exploratory and hypothesis-generating rather than evidence that the identified clusters are clinically actionable or associated with improved outcomes.
The findings build on earlier work suggesting that canine HSA arises from multipotent progenitors that differentiate into distinct subtypes, with prior NGS-based studies identifying mutations in P53, PIK3CA, ATRX, and NRAS that predicted better responses to targeted therapies. The present study adds to this growing body of evidence by demonstrating that expression-based stratification is feasible using FFPE samples, which could help make molecular profiling more accessible in clinical practice.
The authors conclude that molecular profiling of canine HSA substantiates the significance of precision oncology in veterinary medicine, potentially enhancing treatment efficacy while facilitating better management of side effects. However, they emphasize that larger independent cohorts with prospective treatment and follow-up data will be necessary to determine the reproducibility, prognostic significance, and predictive utility of these molecular subsets.
