FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting
Abstract Background The N-formyl peptide receptor family (FPRs) is implicated in the progression of diverse cancer types, yet studies specifically exploring their roles in breast cancer remain scarce. Methods A comprehensive analysis integrating bulk RNA-seq transcriptomics, methylomics, single-cell...
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2025-08-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03942-4 |
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| author | Ying Chen Xin Tang Liran Zhu Yi Wang Gaopeng Li Wulin Yang |
| author_facet | Ying Chen Xin Tang Liran Zhu Yi Wang Gaopeng Li Wulin Yang |
| author_sort | Ying Chen |
| collection | DOAJ |
| description | Abstract Background The N-formyl peptide receptor family (FPRs) is implicated in the progression of diverse cancer types, yet studies specifically exploring their roles in breast cancer remain scarce. Methods A comprehensive analysis integrating bulk RNA-seq transcriptomics, methylomics, single-cell transcriptomics, and spatial single-cell transcriptomics data was conducted to elucidate the distinctive characteristics of FPRs in breast cancer. This study particularly focused on delineating the e xpression profiles of FPR3 across distinct breast cancer subtypes, while systematically investigating its prognostic implications and association with macrophage polarization patterns in breast cancer patients. Furthermore, molecular docking analysis was performed to screen potential therapeutic compounds targeting FPR3, providing insights into its druggability. Results Notably, FPR3 was found to be highly expressed in macrophages within breast cancer tissues, with a notably elevated level in HER2-positive and triple-negative breast cancer (TNBC) subtypes, both of which are associated with poor prognosis. FPR3 expression inversely correlates with promoter methylation levels. Further analysis of pan-cancer immune infiltration patterns uncovered a striking association between FPR3 and macrophage infiltration, as well as their polarization status. Knockdown of FPR3 expression in macrophages markedly enhanced the expression of IL6, TNF-α, and TGF-β, while significantly reducing IL10 levels, indicative of a shift towards an M1-like macrophage phenotype. Through computational molecular docking analyses, Otamixaban and Rivaroxaban emerged as promising candidate inhibitors of FPR3. Conclusions These findings underscore the profound infiltration of FPR3 + macrophages in breast cancer patients with adverse prognoses, highlighting FPR3 as a potential therapeutic target for intervening breast cancer aggressiveness. |
| format | Article |
| id | doaj-art-c1766f8a49bb477ca24dd7afb12c4a87 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
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| series | Cancer Cell International |
| spelling | doaj-art-c1766f8a49bb477ca24dd7afb12c4a872025-08-20T03:47:12ZengBMCCancer Cell International1475-28672025-08-0125111610.1186/s12935-025-03942-4FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targetingYing Chen0Xin Tang1Liran Zhu2Yi Wang3Gaopeng Li4Wulin Yang5Department of Breast Surgery, Department of General Surgery, First Affiliated Hospital of Anhui Medical UniversityHefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesHefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesGeneral Surgery Department, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical UniversityGeneral Surgery Department, Tongji Shanxi Hospital, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical UniversityHefei Cancer Hospital of CAS, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of SciencesAbstract Background The N-formyl peptide receptor family (FPRs) is implicated in the progression of diverse cancer types, yet studies specifically exploring their roles in breast cancer remain scarce. Methods A comprehensive analysis integrating bulk RNA-seq transcriptomics, methylomics, single-cell transcriptomics, and spatial single-cell transcriptomics data was conducted to elucidate the distinctive characteristics of FPRs in breast cancer. This study particularly focused on delineating the e xpression profiles of FPR3 across distinct breast cancer subtypes, while systematically investigating its prognostic implications and association with macrophage polarization patterns in breast cancer patients. Furthermore, molecular docking analysis was performed to screen potential therapeutic compounds targeting FPR3, providing insights into its druggability. Results Notably, FPR3 was found to be highly expressed in macrophages within breast cancer tissues, with a notably elevated level in HER2-positive and triple-negative breast cancer (TNBC) subtypes, both of which are associated with poor prognosis. FPR3 expression inversely correlates with promoter methylation levels. Further analysis of pan-cancer immune infiltration patterns uncovered a striking association between FPR3 and macrophage infiltration, as well as their polarization status. Knockdown of FPR3 expression in macrophages markedly enhanced the expression of IL6, TNF-α, and TGF-β, while significantly reducing IL10 levels, indicative of a shift towards an M1-like macrophage phenotype. Through computational molecular docking analyses, Otamixaban and Rivaroxaban emerged as promising candidate inhibitors of FPR3. Conclusions These findings underscore the profound infiltration of FPR3 + macrophages in breast cancer patients with adverse prognoses, highlighting FPR3 as a potential therapeutic target for intervening breast cancer aggressiveness.https://doi.org/10.1186/s12935-025-03942-4FPR3Breast cancerMacrophage polarizationImmunity |
| spellingShingle | Ying Chen Xin Tang Liran Zhu Yi Wang Gaopeng Li Wulin Yang FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting Cancer Cell International FPR3 Breast cancer Macrophage polarization Immunity |
| title | FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting |
| title_full | FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting |
| title_fullStr | FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting |
| title_full_unstemmed | FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting |
| title_short | FPR3 orchestrates macrophage polarization in breast cancer: multi-omics dissection of prognostic relevance and therapeutic targeting |
| title_sort | fpr3 orchestrates macrophage polarization in breast cancer multi omics dissection of prognostic relevance and therapeutic targeting |
| topic | FPR3 Breast cancer Macrophage polarization Immunity |
| url | https://doi.org/10.1186/s12935-025-03942-4 |
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