Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets
Abstract Background Transcriptomic features of breast cancer locoregional recurrence (LRR) remain poorly understood. We therefore sought to investigate transcriptomic features associated with LRR in newly diagnosed invasive breast tumors from our institutional dataset. Methods Transcriptomic profili...
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2025-05-01
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| Series: | Breast Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13058-025-01987-x |
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| author | Timothy J. Robinson Casey L. Liveringhouse Christopher Wilson Sam Friedman Justyn Nakashima Matthew N. Mills Jacob D. Purcell Nicholas B. Figura Du Dongliang Ram Thapa Eric Welsh Kamran A. Ahmed G. Daniel Grass Brooke L. Fridley Roberto Diaz |
| author_facet | Timothy J. Robinson Casey L. Liveringhouse Christopher Wilson Sam Friedman Justyn Nakashima Matthew N. Mills Jacob D. Purcell Nicholas B. Figura Du Dongliang Ram Thapa Eric Welsh Kamran A. Ahmed G. Daniel Grass Brooke L. Fridley Roberto Diaz |
| author_sort | Timothy J. Robinson |
| collection | DOAJ |
| description | Abstract Background Transcriptomic features of breast cancer locoregional recurrence (LRR) remain poorly understood. We therefore sought to investigate transcriptomic features associated with LRR in newly diagnosed invasive breast tumors from our institutional dataset. Methods Transcriptomic profiling was performed on 632 tumors from consecutive patients treated within our health system for newly diagnosed non-metastatic breast cancer. Univariable Cox models identified genes whose expression was associated with LRR (q-value < 0.05). Up-regulated (UR) genes were defined as hazard ratio (HR) > 1 and down-regulated (DR) genes were defined as HR < 1. Gene set enrichment analyses were performed for UR and DR gene sets and validated within two external cohorts of ER- tumors. Results With a median follow-up of 7.6 years, we observed 38 LRRs: 28/481 (5.8%) in ER + and 10/151 (6.6%) in ER-. There were 43 UR and 7 DR genes associated with LRR in ER + tumors, while 417 UR and 1150 DR genes were associated with LRR in ER- tumors. UR genes in ER + tumors were enriched for roles in cell proliferation (q < 0.05). In contrast, LRR in ER- tumors was most strongly associated with DR genes enriched for MHC-II-mediated antigen presentation and T cell activation (q < 0.05). In external cohorts of ER- tumors, 97 significant DR genes (p < 0.05) were enriched for 18 pathways, including 5 pathways involved in MHC-II signaling, antigen presentation and T-cell activation. Conclusions Transcriptomic patterns associated with LRR appear distinct between ER + and ER- tumors. In ER + tumors, LRR appears predominantly associated with proliferation, whereas ER- LRR suggests a robust pattern of suppressed antigen presentation via MHC-II. |
| format | Article |
| id | doaj-art-6497f130aab64362aa62746f5c8a82c0 |
| institution | Kabale University |
| issn | 1465-542X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Breast Cancer Research |
| spelling | doaj-art-6497f130aab64362aa62746f5c8a82c02025-08-20T03:53:46ZengBMCBreast Cancer Research1465-542X2025-05-0127111210.1186/s13058-025-01987-xAssociation between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasetsTimothy J. Robinson0Casey L. Liveringhouse1Christopher Wilson2Sam Friedman3Justyn Nakashima4Matthew N. Mills5Jacob D. Purcell6Nicholas B. Figura7Du Dongliang8Ram Thapa9Eric Welsh10Kamran A. Ahmed11G. Daniel Grass12Brooke L. Fridley13Roberto Diaz14Department of Therapeutic Radiology, Yale School of MedicineDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center and Research InstituteBiostatistics and Bioinformatics Shared Resource, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Therapeutic Radiology, Yale School of MedicineDepartment of Therapeutic Radiology, Yale School of MedicineDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center and Research InstituteMichigan State University College of Human MedicineDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center and Research InstituteBiostatistics and Bioinformatics Shared Resource, H. Lee Moffitt Cancer Center and Research InstituteBiostatistics and Bioinformatics Shared Resource, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center and Research InstituteBiostatistics and Bioinformatics Shared Resource, H. Lee Moffitt Cancer Center and Research InstituteDepartment of Radiation Oncology, H. Lee Moffitt Cancer Center and Research InstituteAbstract Background Transcriptomic features of breast cancer locoregional recurrence (LRR) remain poorly understood. We therefore sought to investigate transcriptomic features associated with LRR in newly diagnosed invasive breast tumors from our institutional dataset. Methods Transcriptomic profiling was performed on 632 tumors from consecutive patients treated within our health system for newly diagnosed non-metastatic breast cancer. Univariable Cox models identified genes whose expression was associated with LRR (q-value < 0.05). Up-regulated (UR) genes were defined as hazard ratio (HR) > 1 and down-regulated (DR) genes were defined as HR < 1. Gene set enrichment analyses were performed for UR and DR gene sets and validated within two external cohorts of ER- tumors. Results With a median follow-up of 7.6 years, we observed 38 LRRs: 28/481 (5.8%) in ER + and 10/151 (6.6%) in ER-. There were 43 UR and 7 DR genes associated with LRR in ER + tumors, while 417 UR and 1150 DR genes were associated with LRR in ER- tumors. UR genes in ER + tumors were enriched for roles in cell proliferation (q < 0.05). In contrast, LRR in ER- tumors was most strongly associated with DR genes enriched for MHC-II-mediated antigen presentation and T cell activation (q < 0.05). In external cohorts of ER- tumors, 97 significant DR genes (p < 0.05) were enriched for 18 pathways, including 5 pathways involved in MHC-II signaling, antigen presentation and T-cell activation. Conclusions Transcriptomic patterns associated with LRR appear distinct between ER + and ER- tumors. In ER + tumors, LRR appears predominantly associated with proliferation, whereas ER- LRR suggests a robust pattern of suppressed antigen presentation via MHC-II.https://doi.org/10.1186/s13058-025-01987-xBreast cancerEstrogen receptor negativeImmune responseLocoregional control |
| spellingShingle | Timothy J. Robinson Casey L. Liveringhouse Christopher Wilson Sam Friedman Justyn Nakashima Matthew N. Mills Jacob D. Purcell Nicholas B. Figura Du Dongliang Ram Thapa Eric Welsh Kamran A. Ahmed G. Daniel Grass Brooke L. Fridley Roberto Diaz Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets Breast Cancer Research Breast cancer Estrogen receptor negative Immune response Locoregional control |
| title | Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets |
| title_full | Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets |
| title_fullStr | Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets |
| title_full_unstemmed | Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets |
| title_short | Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets |
| title_sort | association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer retrospective review of multi institutional datasets |
| topic | Breast cancer Estrogen receptor negative Immune response Locoregional control |
| url | https://doi.org/10.1186/s13058-025-01987-x |
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