{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T19:08:08Z","timestamp":1790017688456,"version":"4.0.1"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T00:00:00Z","timestamp":1770249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Breast cancer (BC) is a common malignant tumor with high incidence and mortality rates. Mitophagy refers to a selective form of autophagy that is believed to be closely related to the occurrence and progression of BC. Identifying the mitophagy-related sites associated with BC can help us gain a deeper understanding of the underlying mechanisms of BC, laying the foundation for early diagnosis and effective treatment of BC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>\n                      RNA-seq expression data of BC were obtained from the GEO and TCGA databases. Differentially expressed genes were intersected with mitophagy-related genes from GeneCards to identify BC-associated mitophagy genes. Prognostic biomarkers were screened using Kaplan\u2013Meier (K\u2013M) survival and ROC analyses. Based on mitophagy-related gene expression and survival data, BC patients were classified into high- and low-risk subgroups for immune infiltration and GSEA analyses. Finally, IHC data from the HPA database and\n                      <jats:italic>in vitro<\/jats:italic>\n                      experiments, including siRNA-mediated knockdown, Western blot, CCK-8 proliferation assay, confocal microscopy and drug prediction were performed to validate the expression and biological functions of candidate biomarkers PBK and NEK2.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Through dual validation of K-M survival analysis and ROC diagnosis-treatment efficacy analysis, we ultimately identified 9 mitophagy-related prognostic biomarkers for BC, and found their expression was significantly upregulated in BC tissues. In addition, the results showed that the degree of immune infiltration in the low-risk subgroup was considered higher than that in the high-risk subgroup. Inhibition of PBK and NEK2 will have an inhibitory effect on the proliferation of BC cell. Furthermore, clinicopathological analyses confirmed a genuinely higher risk in the high-risk subgroup, with PBK and NEK2 independently associated with risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study elucidated the prognostic value, immune microenvironment characteristics, and molecular mechanisms of mitophagy in BC, and identified nine mitophagy-related biomarkers. Among them, PBK and NEK2 were experimentally confirmed to promote tumor cell proliferation, providing novel insights for early diagnosis and therapeutic strategies in breast cancer.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1740830","type":"journal-article","created":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T06:46:09Z","timestamp":1770273969000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Comprehensive analysis of mitophagy-related genes reveals prognostic signatures in breast cancer: based on immune landscapes and treatment target predict"],"prefix":"10.3389","volume":"17","author":[{"given":"Hejia","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Occupational Health and Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, 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