Single-cell transcriptome analysis indicates fatty acid metabolism-mediated metastasis and immunosuppression in male breast cancer

Handong Sun, Lishen Zhang, Zhonglin Wang, Danling Gu, Mengyan Zhu, Yun Cai, Lu Li, Jiaqi Tang, Bin Huang, Bakwatanisa Bosco, Ning Li, Lingxiang Wu, Wei Wu, Liangyu Li, Yuan Liang, Lin Luo, Quanzhong Liu, Yanhui Zhu, Jie Sun, Liang Shi, Tiansong Xia, Chuang Yang, Qitong Xu, Xue Han, Weiming Zhang, Jianxia Liu, Dong Meng, Hua Shao, Xiangxin Zheng, Shuqin Li, Hua Pan, Jing Ke, Wenying Jiang, Xiaolan Zhang, Xuedong Han, Jian Chu, Hongyin An, Juyan Ge, Chi Pan, Xiuxing Wang, Kening Li (), Qianghu Wang () and Qiang Ding ()
Additional contact information
Handong Sun: The First Affiliated Hospital with Nanjing Medical University
Lishen Zhang: Nanjing Medical University
Zhonglin Wang: The Second People’s Hospital of Lianyungang
Danling Gu: Nanjing Medical University
Mengyan Zhu: Nanjing Medical University
Yun Cai: Nanjing Medical University
Lu Li: Nanjing Medical University
Jiaqi Tang: Nanjing Medical University
Bin Huang: Nanjing Medical University
Bakwatanisa Bosco: Nanjing Medical University
Ning Li: Nanjing Medical University
Lingxiang Wu: Nanjing Medical University
Wei Wu: Nanjing Medical University
Liangyu Li: Nanjing Medical University
Yuan Liang: Nanjing Medical University
Lin Luo: Nanjing Medical University
Quanzhong Liu: Nanjing Medical University
Yanhui Zhu: The First Affiliated Hospital with Nanjing Medical University
Jie Sun: The First Affiliated Hospital of Soochow University
Liang Shi: The First Affiliated Hospital with Nanjing Medical University
Tiansong Xia: The First Affiliated Hospital with Nanjing Medical University
Chuang Yang: The First Affiliated Hospital with Nanjing Medical University
Qitong Xu: The First Affiliated Hospital with Nanjing Medical University
Xue Han: The First Affiliated Hospital with Nanjing Medical University
Weiming Zhang: The First Affiliated Hospital with Nanjing Medical University
Jianxia Liu: The First Affiliated Hospital of Soochow University
Dong Meng: Affiliated Hospital of Jiangnan University
Hua Shao: The Second People’s Hospital of Lianyungang
Xiangxin Zheng: Affiliated Suqian Hospital of Xuzhou Medical University
Shuqin Li: The Affiliated Lianyungang Hospital of Xuzhou Medical University
Hua Pan: Liyang People’s Hospital
Jing Ke: The Affiliated Hospital of Nantong University
Wenying Jiang: The Third Affiliated Hospital of Soochow University
Xiaolan Zhang: The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University
Xuedong Han: Nanjing Medical University
Jian Chu: the First People’s Hospital of Yancheng
Hongyin An: the First People’s Hospital of Yancheng
Juyan Ge: The Second People’s Hospital of Lianyungang
Chi Pan: Zhejiang University, College of Medicine
Xiuxing Wang: Nanjing Medical University
Kening Li: Nanjing Medical University
Qianghu Wang: Nanjing Medical University
Qiang Ding: The First Affiliated Hospital with Nanjing Medical University

Nature Communications, 2023, vol. 14, issue 1, 1-18

Abstract: Abstract Male breast cancer (MBC) is a rare but aggressive malignancy with cellular and immunological characteristics that remain unclear. Here, we perform transcriptomic analysis for 111,038 single cells from tumor tissues of six MBC and thirteen female breast cancer (FBC) patients. We find that that MBC has significantly lower infiltration of T cells relative to FBC. Metastasis-related programs are more active in cancer cells from MBC. The activated fatty acid metabolism involved with FASN is related to cancer cell metastasis and low immune infiltration of MBC. T cells in MBC show activation of p38 MAPK and lipid oxidation pathways, indicating a dysfunctional state. In contrast, T cells in FBC exhibit higher expression of cytotoxic markers and immune activation pathways mediated by immune-modulatory cytokines. Moreover, we identify the inhibitory interactions between cancer cells and T cells in MBC. Our study provides important information for understanding the tumor immunology and metabolism of MBC.

Date: 2023
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DOI: 10.1038/s41467-023-41318-2

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