Chromatin run-on sequencing analysis finds that ECM remodeling plays an important role in canine hemangiosarcoma pathogenesis

Background Canine visceral hemangiosarcoma (HSA) is a highly aggressive cancer of endothelial origin that closely resembles visceral angiosarcoma in humans, both clinically and histopathologically. Currently there is an unmet need for new diagnostics and therapies for both forms of this disease. The goal of this study was to utilize ChRO-seq and immunohistochemistry (IHC) to identify gene and protein expression signatures that may be important drivers of HSA progression. Methods Chromatin run-on sequencing (ChRO-seq) was performed on tissue isolated from 17 HSA samples and 4 normal splenic samples. Computational analysis was then used to identify differentially expressed genes and these factors were subjected to gene ontology analysis. Next, RT-PCR was performed on a subset of candidate genes to validate the ChRO-seq data. We then performed Masson’s trichrome, H&E, and IHC staining on these tissues to investigate morphological features of HSA tumor tissue as well as the expression patterns of several proteins identified in our ChRO-seq analysis. Results ChRO-seq analysis revealed over a thousand differentially expressed genes in HSA tissue compared with normal splenic tissue (FDR