STEAP4+ neutrophils: a promising circulating biomarker for lung metastasis

Ai, C.; Wu, H.; Yang, H.; Wang, J.; Liu, C.; Ng, M. S. F.; Zhou, Z.; Zhuang, F.; Gao, Q.; Wang, L.; Shi, C.; Zhu, L.; Bu, Z.; Chen, C.; Ng, L. G.; Zhang, Z.

doi:10.64898/2025.12.27.696660

bioRxiv · 10.64898/2025.12.27.696660

STEAP4+ neutrophils: a promising circulating biomarker for lung metastasis

Ai, C.·Wu, H.·Yang, H.·Wang, J.·Liu, C.·Ng, M. S. F.·Zhou, Z.·Zhuang, F.·Gao, Q.·Wang, L.·Shi, C.·Zhu, L.·Bu, Z.·Chen, C.·Ng, L. G.·Zhang, Z.

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Abstract

As the leading contributor to cancer-related mortality, metastasis often evades detection until advanced stages, underscoring the critical need for early predictive biomarkers. Neutrophils are naturally circulating sentinels that have been implicated in pioneering pre-metastatic niche formation in distant organs. Nevertheless, their heterogeneity within evolving metastatic microenvironments remains poorly characterized. Here, through dynamically delineating neutrophil subsets via single-cell transcriptomics, we identified a conserved feature of lung metastasis in breast cancer and other cancer models. Among the core genes, a cell surface marker, STEAP4, was selected and validated to indicate lung metastases at both RNA and protein levels. In both humans and mice, these STEAP4+ neutrophils were detectable not only in lung metastatases but also in the circulation. Clinically, the abundance of circulating STEAP4+ neutrophils robustly discriminates patients with lung metastasis from those with localized primary tumor. Our findings uncover STEAP4+ neutrophils as a promising biomarker and lay the groundwork for a non-invasive, blood-based diagnostic strategy for metastatic disease.

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Ai, C., Wu, H., Yang, H., Wang, J., Liu, C., Ng, M. S. F., Zhou, Z., Zhuang, F., Gao, Q., Wang, L., Shi, C., Zhu, L., Bu, Z., Chen, C., Ng, L. G., Zhang, Z.. 2025-12-27. STEAP4+ neutrophils: a promising circulating biomarker for lung metastasis. https://doi.org/10.64898/2025.12.27.696660

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