Abstract
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.
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Data availability
The canine clinical trial datasets generated and/or analyzed during the current study are available in the GEO database (RRID:SCR_005012; accession ID: GSE309676). Source data is available in Supplementary Data 2.
Code availability
Codes are deposited at GitHub (https://github.com/Anjaligarg006/NAT.git).
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Acknowledgements
We would like to thank the NCI-COTC member institutions, canine clinical trials teams, and the families who enrolled their dogs into COTC-021/022. We would also like to acknowledge the Molecular Histopathology Laboratory for their assistance with FFPE RNA isolation, and the Genomics Technology Laboratory for their assistance with RNA isolation and the NanoString IO Panel. This research was supported by the Intramural Research Program (Z01-BC006161) of the National Institutes of Health (NIH). The contributions of the NIH author(s) were made as part of their official duties as NIH federal employees, are in compliance with agency policy requirements, and are considered Works of the United States Government. However, the findings and conclusions presented in this paper are those of the author(s) and do not necessarily reflect the views of the NIH or the U.S. Department of Health and Human Services. Figure 1 (https://biorender.com/w5r5qeg), Fig. 2D (https://biorender.com/t9y5khn), and Fig. 5 (https://biorender.com/r7ef8fg) were created in BioRender.
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J.A.B.: conceptualization, methodology, project administration, data curation, investigation, visualization, writing—original draft; A.G.: formal analysis, visualization, writing—review & editing; P.C.: resources, supervision, writing—review & editing; C.M.: data curation, writing—review & editing; A.L.: supervision, project administration, writing—review & editing.
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Beck, J.A., Garg, A., Choyke, P.L. et al. Comprehensive analysis of non-tumor lung, liver, and kidney transcriptomes in canine metastatic osteosarcoma. Commun Biol (2026). https://doi.org/10.1038/s42003-026-09870-x
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DOI: https://doi.org/10.1038/s42003-026-09870-x
