Comparative gene expression profiling identifies common molecular signatures of NF-κB activation in canine and human diffuse large B cell lymphoma (DLBCL)

Manikhandan A. V. Mudaliar, Ross D. Haggart, Gino Miele, Grant Sellar, Karen A. L. Tan, John R. Goodlad, Elspeth Milne, David M. Vail, Ilene Kurzman, Daniel Crowther, David J. Argyle

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    Abstract

    We present the first comparison of global transcriptional changes in canine and human diffuse large B-cell lymphoma (DLBCL), with particular reference to the nuclear factor-kappa B (NF-kappaB) pathway. Microarray data generated from canine DLBCL and normal lymph nodes were used for differential expression, co-expression and pathway analyses, and compared with analysis of microarray data from human healthy and DLBCL lymph nodes. The comparisons at gene level were performed by mapping the probesets in canine microarrays to orthologous genes in humans and vice versa. A considerable number of differentially expressed genes between canine lymphoma and healthy lymph node samples were also found differentially expressed between human DLBCL and healthy lymph node samples. Principal component analysis using a literature-derived NF-kappaB target gene set mapped to orthologous canine array probesets and human array probesets clearly separated the healthy and cancer samples in both datasets. The analysis demonstrated that for both human and canine DLBCL there is activation of the NF-kappaB/p65 canonical pathway, indicating that canine lymphoma could be used as a model to study NF-kappaB-targeted therapeutics for human lymphoma. To validate this, tissue arrays were generated for canine and human NHL and immunohistochemistry was employed to assess NF-kappaB activation status. In addition, human and canine B-cell lymphoma lines were assessed for NF-kappaB activity and the effects of NF-kappaB inhibition.

    Original languageEnglish
    Article numbere72591
    Number of pages17
    JournalPLoS ONE
    Volume8
    Issue number9
    DOIs
    Publication statusPublished - 4 Sep 2013

    Keywords

    • Animals
    • Blotting, Western
    • Dogs
    • Electrophoretic Mobility Shift Assay
    • Humans
    • Immunohistochemistry
    • Lymphoma, Large B-Cell, Diffuse
    • NF-kappa B
    • Oligonucleotide Array Sequence Analysis
    • Tissue Array Analysis
    • Transcriptome

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    Mudaliar, M. A. V., Haggart, R. D., Miele, G., Sellar, G., Tan, K. A. L., Goodlad, J. R., Milne, E., Vail, D. M., Kurzman, I., Crowther, D., & Argyle, D. J. (2013). Comparative gene expression profiling identifies common molecular signatures of NF-κB activation in canine and human diffuse large B cell lymphoma (DLBCL). PLoS ONE, 8(9), [e72591]. https://doi.org/10.1371/journal.pone.0072591