Transcriptomic profiling reveals prognostic gene signatures and immune landscape alterations in canine diffuse large B-cell lymphoma

Canine diffuse large B-cell lymphoma (cDLBCL) is a frequent and highly aggressive hematopoietic malignancy that serves as a robust translational model for human non-Hodgkin lymphomas. However, the molecular determinants underlying disease progression and prognosis remain poorly defined, hindering precise therapeutic decisions. Clarifying these mechanisms is essential to support the development of prognostic tools and targeted interventions in veterinary oncology. This study aimed to identify prognostically relevant genes and immune alterations associated with cDLBCL. RNA-Seq was performed on lymph node samples from 15 dogs with multicentric DLBCL and two healthy controls. Differential gene expression was assessed to identify key molecular alterations. Functional annotation, pathway analysis, and Kaplan–Meier survival correlations were used to characterize the biological and clinical significance of target genes. Additionally, immune cell deconvolution was conducted to explore changes in the tumor microenvironment (TME). Transcriptomic profiling revealed 410 differentially expressed genes (DEGs), comprising 408 downregulated and 2 upregulated genes in tumor samples compared to normal lymph nodes. Among these, STOM, TBC1D8, HMOX1, ABCB1, and CTLA4 emerged as genes of interest due to their involvement in immune regulation, oxidative stress response, vesicular trafficking, drug resistance, and immune checkpoint signaling. Lower expression of these genes was significantly associated with reduced overall survival. Immune infiltration analysis demonstrated a dominance of neoplastic B cells and a marked reduction in cytotoxic T cells and macrophages, consistent with an immunosuppressive TME. This study identifies key molecular and immunological signatures associated with prognosis in cDLBCL, providing insight into mechanisms of immune suppression and therapeutic resistance. The findings reinforce the translational value of canine lymphoma as a model for human disease and support the integration of molecular biomarkers into veterinary oncologic practice to guide individualized treatment strategies.