Gene expression patterns in canine diffuse large B-cell lymphoma

Abstract

Abstract Introduction: Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive form of lymphoma in dogs, closely resembling human DLBCL in its clinical behavior and molecular features. While CHOP chemotherapy is the standard treatment, many dogs experience poor responses or early relapse, underscoring the need for a more comprehensive understanding of the disease’s molecular underpinnings. This study aimed to investigate the gene expression profiles in canine DLBCL to identify potential biomarkers and therapeutic targets. Materials and Methods: Fresh frozen lymph node samples were collected from six dogs diagnosed with DLBCL and four healthy controls. Total RNA was extracted, and RNA sequencing (RNA-seq) was performed to profile global gene expression. Differentially expressed genes were identified using DESeq2, and principal component analysis (PCA) was used to distinguish expression patterns between groups. Key findings were validated using quantitative PCR (qPCR) to confirm the dysregulation of selected genes. Results: RNA-seq analysis revealed 3, 156 differentially expressed genes, including 1, 418 upregulated and 1, 738 downregulated in DLBCL samples. PCA showed distinct clustering between DLBCL and healthy groups, confirming significant gene expression divergence. qPCR analysis validated these results, highlighting the upregulation of genes such as NIT2 (fold change: 3.145; FDR: 0.0074), MYC (fold change: 3.086; FDR: 0.0494), and CDK4 (fold change: 2.151; FDR: 0.0331), suggesting their involvement in tumorigenesis and disease progression. Conversely, genes such as AICDA (fold change: -4.338; FDR: 0.0284), BCL6 (fold change: -2.352; FDR: 0.0469) and CDH1 (fold change: -1.699; FDR: 0.0469) were significantly downregulated, indicating potential suppression of tumor-suppressive pathways. Conclusion: This study provides valuable insights into the molecular mechanisms underlying canine DLBCL. The identification of differentially expressed genes and pathways highlights novel biomarkers and potential therapeutic targets. Moreover, the findings demonstrate the translational relevance of canine DLBCL as a comparative model for human lymphoma, advancing our understanding of both veterinary and human oncology. This abstract was edited and formatted with the assistance of generative artificial intelligence (Chatgpt) to enhance clarity and presentation. Citation Format: Nelly Elshafie, Ekramy SayedAhmed, Michael O. Childress, Andrea Pires dos Santos. Gene expression profiling of canine diffuse large B-cell lymphoma: Insights from RNA sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1439.