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. 2021 Jan 25;12(2):160.
doi: 10.3390/genes12020160.

Transcriptional Differences between Canine Cutaneous Epitheliotropic Lymphoma and Immune-Mediated Dermatoses

Nadja Gerber  1   2   3 , Magdalena A T Brunner  1   2 , Vidhya Jagannathan  2   4 , Tosso Leeb  2   4 , Nora M Gerhards  1   5 , Monika M Welle  1   2 , Martina Dettwiler  1   2
Affiliations

Transcriptional Differences between Canine Cutaneous Epitheliotropic Lymphoma and Immune-Mediated Dermatoses

Nadja Gerber et al. Genes (Basel). .

Abstract

Canine cutaneous epitheliotropic T-cell lymphoma (CETL) and immune-mediated T-cell predominant dermatoses (IMD) share several clinical and histopathological features, but differ substantially in prognosis. The discrimination of ambiguous cases may be challenging, as diagnostic tests are limited and may prove equivocal. This study aimed to investigate transcriptional differences between CETL and IMD, as a basis for further research on discriminating diagnostic biomarkers. We performed 100bp single-end sequencing on RNA extracted from formalin-fixed and paraffin-embedded skin biopsies from dogs with CETL and IMD, respectively. DESeq2 was used for principal component analysis (PCA) and differential gene expression analysis. Genes with significantly different expression were analyzed for enriched pathways using two different tools. The expression of selected genes and their proteins was validated by RT-qPCR and immunohistochemistry. PCA demonstrated the distinct gene expression profiles of CETL and IMD. In total, 503 genes were upregulated, while 4986 were downregulated in CETL compared to IMD. RT-qPCR confirmed the sequencing results for 5/6 selected genes tested, while the protein expression detected by immunohistochemistry was not entirely consistent. Our study revealed transcriptional differences between canine CETL and IMD, with similarities to human cutaneous lymphoma. Differentially expressed genes are potential discriminatory markers, but require further validation on larger sample collections.

Keywords: Canis lupus familiaris; FFPE tissue; RNA sequencing; cutaneous T-cell lymphoma; cytotoxic dermatitis; dog; lupus erythematosus; skin disease; transcriptome.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Figures

Figure A1
Figure A1
Western blot analysis confirming the specific binding of canine TCF7 by the antibody used.
Figure 1
Figure 1
Principal component analysis of the RNA sequencing output. The PCA plot is calculated on the basis of 5000 genes most differentially expressed between canine CETL and IMD skin samples. Distances between samples reflect differences in the transcriptome profile of the samples.
Figure 2
Figure 2
MA plot of the RNA sequencing output. The plot visualizes the differences in gene expression in a log2 ratio (log2FC) between the two groups. Each dot represents a gene; red dots indicate differential expression (FDR < 0.01).
Figure 3
Figure 3
Relative mRNA expression of selected genes resulting from RT-qPCR. IMD cases depicted as green dots, CETL cases as blue squares; whiskers indicate the standard deviation of the mean; ** p < 0.05. The outliers in the IL2RB and ITGB7 measurements are cases no. 3 and 8, and cases no. 8 and 11, respectively.
Figure 4
Figure 4
Results of the immunohistochemistry. Percentage of TCF7- and FOXP3-positive T-cells in the whole skin (overall), in the epithelial structures (epithelium) and the dermal portion (dermis); whiskers indicate the standard deviation of the mean; ** p < 0.05.
See this image and copyright information in PMC

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