Insight into the potential candidate genes and signaling pathways involved in lymphoma disease in dogs using a comprehensive whole blood transcriptome analysis

Sunirmal Sheet; Ye-In Oh; Devender Arora; Bong-Hwan Choi; Minjeong Ko; Yelin Nam; Youngjo Lim; Jin-A Lim; Mirim Park; Woncheoul Park; Kyoung-Won Seo; Kyung-Tai Lee

doi:10.1016/j.gene.2022.146735

Insight into the potential candidate genes and signaling pathways involved in lymphoma disease in dogs using a comprehensive whole blood transcriptome analysis

Gene. 2022 Sep 5:838:146735. doi: 10.1016/j.gene.2022.146735. Epub 2022 Jul 12.

Authors

Affiliations

¹ Animal Genome and Bioinformatics, National Institute of Animal Science, RDA, Wanju 55365, South Korea.
² College of Veterinary Science, Seoul National University, Seoul 08826, South Korea.
³ Bioinformatics Core, Purdue University, West Lafayette, IN 47907, United States.
⁴ Haemaru Referral Animal Hospital, Seongnamsi 13590, South Korea.
⁵ College of Veterinary Science, Seoul National University, Seoul 08826, South Korea. Electronic address: kwseo@snu.ac.kr.
⁶ Animal Genome and Bioinformatics, National Institute of Animal Science, RDA, Wanju 55365, South Korea. Electronic address: leekt@korea.kr.

PMID: 35835403
DOI: 10.1016/j.gene.2022.146735

Abstract

Lymphoma is one of the most prevalent hematological cancers, accounting for 15-20 % of new cancer diagnoses in dogs. Therefore, this study aims to explore the important genes and pathways involved in canine lymphoma progression and understand the underlying molecular mechanisms using RNA sequencing. In this study, RNAs acquired from seven pairs of lymphoma and non-lymphoma blood samples were sequenced from different breeds of dogs. Sequencing reads were preprocessed, aligned with the reference genome, assembled and expressions were estimated through bioinformatics approaches. At a false discovery rate (FDR) < 0.05 and fold change (FC) ≥ 1.5, a total of 625 differentially expressed genes (DEGs) were identified between lymphoma and non-lymphoma samples, including 347 up-regulated DEGs such as SLC38A11, SCN3A, ZIC5 etc. and 278 down-regulated DEGs such as LOC475937, CSMD1, KRT14 etc. GO enrichment analysis showed that these DEGs were highly enriched for molecular function of ATP binding and calcium ion binding, cellular process of focal adhesion, and biological process of immune response, and defense response to virus. Similarly, KEGG pathways analysis revealed 11 significantly enriched pathways such as ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, ABC transporters etc. In the protein-protein interaction (PPI) network, CDK1 was found to be a top hub gene with highest degree of connectivity. Three modules selected from the PPI network showed that canine lymphoma was highly associated with cell cycle, ECM-receptor interaction, hypertrophic cardiomyopathy, dilated cardiomyopathy and RIG-I-like receptor signaling pathway. Overall, our findings highlighted new candidate therapeutic targets for further testing in canine lymphoma and facilitate the understanding of molecular mechanism of lymphoma's progression in dogs.

Keywords: Canine lymphoma; Enrichment analysis; Hematological cancers DEGs; Hub gene; Module analysis; PPI network; Pathway-network; RNA sequencing; Whole blood.

MeSH terms

Animals
Computational Biology
Dogs
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Gene Regulatory Networks
Phosphatidylinositol 3-Kinases* / genetics
Protein Interaction Maps / genetics
Signal Transduction / genetics
Transcriptome