Comprehensive analysis of non-tumor lung, liver, and kidney transcriptomes in canine metastatic osteosarcoma.

The non-tumor tissue adjacent to metastases can appear morphologically unremarkable under a microscope; however, it is exposed to a milieu of secretory factors and proteins derived from tumor cells, stromal cells, and immune cells within the surrounding tumor microenvironment. Studies investigating the peritumoral tissue (PTT) or so-called Normal tissue Adjacent to Tumor tissue (NAT) have identified distinct differences between the genomic and transcriptomic profiles of healthy and tumor-adjacent non-tumor tissues. These alterations are hypothesized to have significant implications in local tumor progression, metastasis, and patient outcome. Most NAT/PTT studies focus on the primary tumor microenvironment (TME) with comparisons between patients with and without cancer. The study described herein expands upon this work by investigating the metastatic TME with comparisons between met-recipient and met-free tissues, both derived from a canine osteosarcoma clinical trial. Our study identifies shared and tissue-specific changes in met-recipient non-tumor lung, liver, and kidney which overlap with transcriptional alterations described in human cancers. These findings improve our understanding of the landscape of the peritumoral TME of metastatic osteosarcoma and further underscore the translational relevance of the canine patient as a model of human disease.