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

Sep 22, 2026

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The study examines peritumoral tissue adjacent to canine osteosarcoma metastases to clarify how non-tumor lung, liver, and kidney transcriptomes change within the metastatic tumor microenvironment. It contrasts met-recipient tissues with met-free tissues collected from the same canine clinical trial, avoiding confounding between cohorts. The work links transcriptional alterations in adjacent tissues to shared and tissue-specific patterns also described in human cancers, improving understanding of metastatic progression and supporting translational relevance of the canine model.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Background

Peritumoral tissue (PTT) and NAT/PTT concepts

Limitations of primary-tumor-only comparisons

Study design

Met-recipient and met-free tissue comparisons

Clinical trial-based tissue sourcing

Rationale and implications

Links to local metastatic progression and outcomes

Cross-species relevance to human cancer signatures

communications biology Article | A Nature Portfolio journal | | | | --- | --- | --- | | [https://doi.org/10.1038/s42003-026-09870-x](https://doi.org/10.1038/s42003-026-09870-x) | | | | Comprehensive analysis of non-tumor lung, liver, and kidney transcriptomes incanine metastatic osteosarcoma
Check for updates | | | | Jessica A. Beck 1,2 , Anjali Garg 2, Peter L. Choyke3, Christina Mazcko2 & Amy K. LeBlanc 2 | | | | 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-tumortissues. These alterations are hypothesizedto 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. | | | | Osteosarcoma is a rare cancer of bone that primarily affects pediatric and adolescent patients1. While local tumor control strategies have a high success rate, thereis a critical unmet need for therapies targeting metastatic disease2. Cellular and stromal components within the tumor microenvironment (TME) provide therapeutic opportunities for promoting anti-tumor responses; examples include treatments that target pro-tumor mechanisms (e.g., angiogenesis3, ﬁbroblasts and ﬁbrosis4, and immune checkpoint proteins5) or those that enhance anti-tumor activities (e.g., CAR T-cell therapy6). A better understanding of the peritumoral TME of metastatic disease will provide important context to mechanisms of metastatic progression in support ofefforts to identify novel therapeutic targets for patients with metastatic osteosarcoma.
With the scarcity ofhuman samples in rare but devastating cancers like osteosarcoma, cell-based studies and informative animal models are vital for the advancement of osteosarcoma research7,8. Canine patients develop spontaneous osteosarcoma in their natural lifespan with strong biologic similarities to that of human osteosarcoma9. The presence of metastases is the primary determinant ofoutcome in bothpatient populations. In the dog, | approximately 75% of appendicular osteosarcomas will metastasize to the lung, 30% to the kidney, and 15% to the liver9. The predilection for metastasis to the lung is also well-documented in human osteosarcoma patients10. Without conﬁrmation at autopsy, the incidence of extrapulmonary metastases may be underappreciated in human patients11. Incanine clinical trials, postmortem examinations are relatively common and allow for the collection ofmetastases and adjacent non-tumor tissues which facilitates the establishment of biobanks9; these multi-institutional efforts support studies investigating the functions of non-tumor tissue in osteosarcoma biology.
Although tissue adjacent to tumors may appear morphologically normal, it demonstrates a variety of subtle changes12, 13. In human patients, many of the ﬁrst studies of cancer-adjacent non-tumor tissue were focused on breast cancer14–16. Data from The C

FAQs

What is the purpose of analyzing non-tumor tissue near osteosarcoma metastases?

The analysis clarifies how peritumoral tissues, though morphologically normal, undergo genomic and transcriptomic changes driven by tumor, stromal, and immune factors within the tumor microenvironment.

How does this study define met-recipient and met-free tissues?

Met-recipient tissues come from osteosarcoma patients with metastases, while met-free tissues are derived from osteosarcoma patients without metastases, enabling a focus on local metastatic presence.

Why is using tissues from the same canine clinical trial important?

All samples originate from a single canine trial, reducing confounding variables such as batch effects or biases from differing preparation or data-collection pipelines.

Sep 22, 2026

Upload by Levi