Fig 1.
Typical histologies of canine soft tissue sarcomas.
Hematoxylin and eosin-stained paraffin sections of canine soft tissue sarcoma tumors, showing typical morphologies of fibrosarcomas (FS), peripheral nerve sheath tumors (PNST) and perivascular wall tumors (PWT).
Fig 2.
Clustering of canine soft tissue sarcoma tumor samples using gene expression patterns.
A) A heat map showing upregulated genes in red and downregulated genes in blue of 2387 tumor-type specific genes. Dendrograms show results of unsupervised hierarchical clustering of samples and genes. B) Principal component analysis of 16 canine soft tissue sarcomas using the 250 most significantly different genes associated with each tumor type. Values are z-scores of expression for each gene. Asterisks indicate reassigned samples.
Table 1.
Individual tumor type’s top 25 genes with the most significantly higher or lower expression.
Genes listed are increased (up) and decreased (down) differentially expressed genes (DEGs) identified using DESeq to compare expression levels of genes in one tumor type against that for both other tumor types. All DEGs were identified using a minimum significance of padj < .05 and a fold change of greater than 2. The 25 genes in each group with the greatest significance determined using adjusted p values are shown. Genes listed in bold were cross referenced with the term “cancer” in at least 50 published manuscripts.
Fig 3.
Comparative gene expression analysis of canine soft tissue sarcomas and human cells, tissues and tumors.
A) Dot plots showing results of gene set over-representation analysis of canine soft tissue sarcoma tumor-type specific DEGs using databases for human tissues and cell lines. B) Plots of Akaike weights obtained using normalized gene expression levels of canine soft tissue sarcoma tumor-type specific DEGs and the same genes expressed in various human soft tissue sarcomas obtained from the NCBI Genomic Data Commons. Abbreviations are: DL: dedifferentiated liposarcomas, FM: fibromyxosarcoma, LMS: leiomyosarcoma, MFH: undifferentiated pleomorphic sarcoma, MPNST: malignant peripheral nerve sheath tumors, SSC: synovial sarcoma, US: undifferentiated pleomorphic sarcoma.
Fig 4.
Common transcription factors associated with gene alterations in canine soft tissue sarcomas compared to normal tissues.
The top 12 most significant common transcription factors identified from a gene set enrichment analysis using lists of tumor-type specific up (A) and down (B) regulated DEGs is shown for each tumor type. Lengths of bars represent the statistical significance of each association, and colors indicate if the results imply upregulation (blue) or downregulation (orange) of the activity of each transcription factor.
Fig 5.
Tumor-type specific transcription factors associated with gene alterations in canine soft tissue sarcomas compared to normal tissues.
The top 14 most significant tumor-type specific transcription factors identified from a gene set enrichment analysis using lists of tumor-type specific up (A) and down (B) regulated DEGs. Values for “Genes” and dot sizes represent the number of DEGs matched to each transcription factor listed.