Single-cell multi-omics analysis reveals two molecular subtypes of human male breast cancer with distinct neuroendocrine and immune characteristics
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Updated: May 19, 2026
Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Handong Sun1, Ruilin Wang2, Zhonglin Wang3
1Department of Breast, Women's Hospital of Nanjing Medical University, Nanjing Women and Children's Healthcare Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
Introduction:
Male breast cancer (MBC) is a rare and malignant disease with limited molecular understanding. There is still no specific therapeutic strategy for patients with MBC in the clinic, the current treatment options for MBC still mainly refer to those of female breast cancer (FBC).
Objectives:
This study aims to report a comprehensive dissection of MBC at the single-cell resolution is urgently required to elucidate the underlying mechanisms of MBC, providing a basis and novel insights into molecular subtypes and developing innovative treatment options for patients with MBC.
Methods:
In this study, we accumulated and analyzed large-scale multi-omics datasets from MBC patients to elucidate the molecular landscape of tumor development at different levels of multi-omics layers.
Results:
Using single-cell RNA sequencing, bulk RNA sequencing, and imaging mass cytometry analysis, we identified two major molecular subtypes of MBC with distinct neuroendocrine (NE) and immune states, and CD45+/KRT18+ cells were present in human MBC. MBC with a high NE score tends to exhibit more aggressive clinical performance, including lymph node metastasis and vascular invasion. Furthermore, we identified a key transcription factor, DLX2, which potentially regulates the NE features of MBC. Cell-cell communication between NPY+ and NPY1R+ cells may also promote NE features. Moreover, we identified that MBC with high NE features was a "cold tumor" and may not be suitable for immunotherapy. Instead, BCL2 may be a potential therapeutic target for MBC with NE features.
Conclusions:
Our study enhances the understanding of MBC and provides valuable insights into clinical diagnosis and therapy.
Insights
Male breast cancer (MBC) is rare, with limited molecular understanding. This study reveals two subtypes, one aggressive with neuroendocrine features, suggesting BCL2 as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Male breast cancer (MBC) is a rare malignancy with poorly understood molecular characteristics.
- Current treatments for MBC are largely adapted from female breast cancer (FBC) protocols, lacking specific therapeutic strategies.
Purpose of the Study:
- To perform a comprehensive, single-cell resolution analysis of MBC to uncover underlying mechanisms.
- To identify novel molecular subtypes and potential therapeutic targets for MBC.
Main Methods:
- Analysis of large-scale multi-omics datasets from MBC patients.
- Utilized single-cell RNA sequencing, bulk RNA sequencing, and imaging mass cytometry.
Main Results:
- Identified two major MBC molecular subtypes: neuroendocrine (NE) and immune-dominant.
- High NE score in MBC correlates with aggressive features like lymph node metastasis and vascular invasion.
- Discovered DLX2 as a key transcription factor regulating NE features and identified BCL2 as a potential therapeutic target for NE-subtype MBC.
Conclusions:
- This research deepens the understanding of MBC's molecular landscape.
- Provides crucial insights for improved clinical diagnosis and novel therapeutic strategies for male breast cancer.
