STEAP4+ neutrophils: a promising circulating biomarker for lung metastasis

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.