Multiplatform single-cell and spatial transcriptomics reveal sex-specific malignant states and architecture in male breast cancer.

Authors

Haoyuan Shi, Xiuli Zhang, Shouliang Cai, Baoku Xu, Haibo Wang, Jian Cui, Zitong Yang, Siyi Chen, Zhangjian Zhou, Shuqun Zhang, Yifan Cai, Yu Zhang, Liling Zhu, Jiandong Wang, Nianzeng Xing

Published in

Science advances. Volume 12. Issue 39. Pages eaeg7722. Sep 25, 2026. Epub Sep 25, 2026.

Abstract

Male breast cancer (MBC) is rare and remains largely managed using knowledge derived from female breast cancer. Here, we generated a multiplatform single-cell and spatial transcriptomic atlas integrating scRNA-seq, SeekSpace, Visium HD, Xenium In Situ, and multiplex immunohistochemistry data from male and female breast cancer cohorts, covering more than 660,000 cells. We identified male-specific tumor cells (MSTCs) that were enriched in MBC, rare in female breast cancer, and associated with poorer disease-free survival. MSTCs exhibited neural transcriptional programs, increased transcriptome-inferred copy number variation burden, and spatial coupling with fatty acid metabolism signals. MSTC-enriched regions showed reduced antigen-presentation signatures and spatial association with APOE⁺/CD163⁺ macrophages, with GRN-SORT1 emerging as a candidate macrophage-tumor interaction axis. These findings define an MBC-associated malignant state and its immune-metabolic spatial context.

PMID:
42789703
Bibliographic data and abstract were imported from PubMed on 26 Sep 2026.

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