FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting

Ying Chen ¹, Xin Tang ^2,3, Liran Zhu ^4,5,6

¹Department of Breast Surgery, Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
²Hefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China.
³Science Island Branch, Graduate School of University of Science and Technology of China, Hefei, 230031, China.
⁴Hefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China. liranzhu@mail.ustc.edu.cn.
⁵Anhui Institute of Pediatric Research, Anhui Provincial Children's Hospital, Children's Hospital of Fudan University Anhui Hospital, Children's Medical Center of Anhui Medical University), Wangjiang Road, Hefei, 230051, Anhui, China. liranzhu@mail.ustc.edu.cn.
⁶Science Island Branch, Graduate School of University of Science and Technology of China, Hefei, 230031, China. liranzhu@mail.ustc.edu.cn.
⁷General Surgery Department, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, China.
⁸General Surgery Department, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, China. malone2001@163.com.
⁹Hefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China. yangw@cmpt.ac.cn.
¹⁰Science Island Branch, Graduate School of University of Science and Technology of China, Hefei, 230031, China. yangw@cmpt.ac.cn.
¹¹Institute of Health and Medical Technology, Hefei Institutes of Physical Science, CAS, No. 350, Shushanhu Road, Hefei, 230031, Anhui, China. yangw@cmpt.ac.cn.

⁰Department of Breast Surgery, Department of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.

Cancer Cell International +

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August 19, 2025

View abstract on PubMed

Summary

N-formyl peptide receptor 3 (FPR3) is highly expressed in breast cancer macrophages, particularly in aggressive subtypes. Targeting FPR3 may offer a new therapeutic strategy for breast cancer treatment.

Area Of Science

Oncology
Immunology
Molecular Biology

Background

The N-formyl peptide receptor family (FPRs) plays a role in various cancers, but their specific function in breast cancer is underexplored.
Limited research exists on FPRs' involvement in breast cancer progression and therapeutic targeting.

Purpose Of The Study

To investigate the expression patterns and prognostic significance of FPR3 in breast cancer.
To explore the association between FPR3, macrophage polarization, and breast cancer subtypes.
To identify potential therapeutic agents targeting FPR3.

Main Methods

Integrated analysis of bulk and single-cell RNA-seq, methylomics, and spatial transcriptomics data.
Investigated FPR3 expression in breast cancer subtypes and its correlation with methylation and immune infiltration.
Performed molecular docking to screen FPR3 inhibitors.

Main Results

FPR3 is highly expressed in breast cancer-associated macrophages, especially in HER2-positive and triple-negative breast cancer (TNBC).
FPR3 expression correlates inversely with promoter methylation and is linked to macrophage infiltration and M1-like polarization.
Otamixaban and Rivaroxaban were identified as potential FPR3 inhibitors via molecular docking.

Conclusions

FPR3-expressing macrophages are prevalent in poor-prognosis breast cancer.
FPR3 represents a potential therapeutic target for mitigating breast cancer aggressiveness.

Keywords:

Breast cancer FPR3 Immunity Macrophage polarization