Efferocytosis-related signatures identified via Single-cell analysis and machine learning predict TNBC outcomes and immunotherapy response

Triple-negative breast cancer (TNBC) is characterized by poor prognosis and limited targeted treatment options. Efferocytosis, an essential immune mechanism for the clearance of apoptotic cells, is increasingly recognized as a key contributor to tumor immune evasion. This study aimed to identify key efferocytosis-related genes in TNBC, investigate their impact on the tumor microenvironment and immunotherapy responses, and construct a prognostic model to inform and optimize treatment strategies. RNA sequencing data and clinical information for patients with TNBC were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Machine learning models were employed to derive efferocytosis-related signatures to predict clinical outcomes and immunotherapy responses. Eight efferocytosis-related genes were identified, considered efferocytosis-related gene signatures herein: P2RX1, IFNG, IL1A, CD93, XKR8, SIAH2, F2RL1, and TLR4. Using the individual risk scores derived from this model, patients were stratified into high- and low-risk groups, revealing significant differences in immune infiltration and immuno-therapy response. Our study highlights the predictive significance of efferocytosis in assessing chemotherapy sensitivity, emphasizing the pivotal role of the immune microenvironment in mediating drug resistance. Moreover, we identified potential targets for immunotherapeutic strategies in the treatment of TNBC.

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Publication Details

Journal
Scientific Reports
Published
2025-11-06
DOI
https://doi.org/10.1038/s41598-025-22816-3
Primary Topic
Phagocytosis and Immune Regulation
Type
article
Field-Weighted Citation Impact
0.00

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article

Efferocytosis-related signatures identified via Single-cell analysis and machine learning predict TNBC outcomes and immunotherapy response

Yiqing You, Wei Lan, Xiran He, Xiaobing Zhu et al.
Scientific Reports
Phagocytosis and Immune Regulation
article

Efferocytosis-related signatures identified via Single-cell analysis and machine learning predict TNBC outcomes and immunotherapy response

Yiqing You, Wei Lan, Xiran He, Xiaobing Zhu, Mengxin Sun, Tingting Dang, S. P. Wen, Tao Zeng, Jiafeng Tang, Shiyu Yang, Xiaolu Li, Liang Zhang, Yan Zhang, Qian Li, Liuyang Zhao, Haoli Sun
article en

Abstract

Triple-negative breast cancer (TNBC) is characterized by poor prognosis and limited targeted treatment options. Efferocytosis, an essential immune mechanism for the clearance of apoptotic cells, is increasingly recognized as a key contributor to tumor immune evasion. This study aimed to identify key efferocytosis-related genes in TNBC, investigate their impact on the tumor microenvironment and immunotherapy responses, and construct a prognostic model to inform and optimize treatment strategies. RNA sequencing data and clinical information for patients with TNBC were obtained from The Cancer Genome Atlas and the Gene Expression Omnibus databases. Machine learning models were employed to derive efferocytosis-related signatures to predict clinical outcomes and immunotherapy responses. Eight efferocytosis-related genes were identified, considered efferocytosis-related gene signatures herein: P2RX1, IFNG, IL1A, CD93, XKR8, SIAH2, F2RL1, and TLR4. Using the individual risk scores derived from this model, patients were stratified into high- and low-risk groups, revealing significant differences in immune infiltration and immuno-therapy response. Our study highlights the predictive significance of efferocytosis in assessing chemotherapy sensitivity, emphasizing the pivotal role of the immune microenvironment in mediating drug resistance. Moreover, we identified potential targets for immunotherapeutic strategies in the treatment of TNBC.

Scientific ReportsVol. 15(1)
Dalian Medical University (CN), Runze (China) (CN), Second Affiliated Hospital of Chongqing Medical University (CN), Ministry of Education (TH), Chongqing Emergency Medical Center (CN), Chongqing Medical University (CN)
National Natural Science Foundation of China, China Postdoctoral Science Foundation, Natural Science Foundation of Chongqing, Centre Scientifique et Technique du Bâtiment
Openalex Percentile: Top 65%
Phagocytosis and Immune Regulation
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