Single-cell Multiomics Profiling Reveals Tumor Microenvironment Landscape and Sex-specific Immune-suppressive Feature in Male Breast Cancer
Year: 2026
Type: other
Abstract: Male breast cancer (MBC) represents a small proportion of all breast cancer (BC) cases, yet it is characterized by a higher rate of lymph node metastasis and poorer prognosis compared to female breast cancer (FBC). However, limited research has been conducted on MBC primarily due to its rarity and the technological constraints. To address this, we performed single-nucleus RNA sequencing (snRNA-seq) on samples from 16 MBC patients (87,518 cells) and imaging mass cytometry (IMC) on samples from 42 patients (265,137 cells), enabling a comprehensive analysis of the MBC microenvironment at both single-cell transcriptome and protein levels. Regarding autosomal regulation, the MBC tumor cells and their microenvironment exhibit distinct characteristics. We found that elevated PBK expression in MBC tumor cells enhances their proliferation, whereas increased SOX4 expression in endothelial cells promotes endothelial-mesenchymal transition (EndMT) and enhances tumor metastatic potential. Additionally, IMC analysis revealed notable differences in the spatial features of the tumor microenvironment between MBC and FBC. Regarding sex-chromosomal regulation, the KDM5D gene originating from the Y chromosome might play a role in altering the tumor microenvironment by regulating the expression of cGAS/STING proteins and reducing immune cell infiltration in MBC. In conclusion, both autosomal and sex-chromosomal regulation collectively contribute to the modulation of microenvironmental differences between MBC and FBC. Our findings offer valuable insights into the mechanisms underlying the unique microenvironments and clinical manifestations of MBC.
Topic: Male Breast Health Studies
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7166300321
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