# Extraction of a stromal metastatic gene signature in breast cancer via spatial profiling

**Authors:** Giorgio Bertolazzi, Valeria Cancila, Davide Vacca, Beatrice Belmonte, Daniele Lecis, Parsa Sirati Moghaddam, Arianna Di Napoli, Mario Paolo Colombo, Giancarlo Pruneri, Giannino Del Sal, Giorgio Scita, Matteo Fassan, Andrea Vecchione, Silvio Bicciato, Claudio Tripodo

PMC · DOI: 10.1186/s13046-025-03353-3 · Journal of Experimental & Clinical Cancer Research : CR · 2025-03-08

## TL;DR

This study identifies a stromal gene signature linked to breast cancer metastasis using spatial profiling, offering a new way to understand and predict metastatic behavior.

## Contribution

The novel contribution is the discovery and validation of a stromal metastatic gene signature in breast cancer using spatial transcriptomics.

## Key findings

- A stromal metastatic gene signature was identified through spatially resolved transcriptomics in breast cancer.
- The signature was validated across human breast cancer datasets and a murine model.
- The stromal Met signature may serve as a prognostic tool for metastatic breast cancer.

## Abstract

The identification of molecular features characterizing metastatic disease is a critical area of oncology research, as metastatic foci often exhibit distinct biological behaviors compared to primary tumors. While the focus has largely been on the neoplastic cells themselves, the characterization of the associated stroma remains largely underexplored, with significant implications for understanding metastasis.

By employing spatially resolved transcriptomics, we analyzed the transcriptional features of primary breast adenocarcinoma and its associated metastatic foci, on a representative set of microregions. We identified a stromal metastatic (Met) signature, which was subsequently validated across transcriptomic reference human breast cancer (BC) datasets and in spatial transcriptomics of a murine model.

We discuss the potential of a stromal Met signature to pinpoint metastatic breast cancer, serving as a prognostic tool that can provide a foundation for the exploration of tumor-extrinsic molecular hallmarks of BC metastatic foci.

The online version contains supplementary material available at 10.1186/s13046-025-03353-3.

## Linked entities

- **Diseases:** breast cancer (MONDO:0004989)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Diseases:** disease (MESH:D004194), metastasis (MESH:D009362), tumor (MESH:D009369), BC (MESH:D001943)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC11892262/full.md

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Source: https://tomesphere.com/paper/PMC11892262