Cross-Species Transcriptomic and Network Analysis of Human and Canine Diffuse Large B-Cell Lymphoma Identifies a...

Area of Science:

• Comparative oncology
• Molecular biology
• Genomics

Background:

• Rational drug selection for canine diffuse large B-cell lymphoma (DLBCL) is limited.
• Human DLBCL research has advanced molecular understanding, but cross-species application is challenging.

Purpose of the Study:

• To investigate conserved transcriptional networks between human and canine DLBCL.
• To identify potential therapeutic targets and biomarkers for canine DLBCL based on shared molecular pathways.

Main Methods:

• Analysis of public human and canine DLBCL transcriptomes to derive a cross-species gene module.
• Projection of the module onto pathway and protein-protein interaction (PPI) networks.
• Querying the Connectivity Map/LINCS library and profiling extracellular-vesicle microRNAs (EV-miRNAs).

Main Results:

• A 409-gene module dominated by DNA replication and cell-cycle checkpoint pathways was identified, centered on TOP2A and PARP1.
• Topoisomerase II poisons and PARP inhibitors showed high potential based on connectivity mapping.
• A module score effectively distinguished tumor from normal tissues and correlated with patient survival in both species.

Conclusions:

• Conserved transcriptional networks in DLBCL suggest topoisomerase II poisons and PARP inhibitors as promising canine therapies.
• Module scores and EV-miRNAs represent potential biomarkers for canine DLBCL treatment and prognosis.