429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry Imaging
OBJECTIVES/GOALS: Metastasis to regional areas decreases invasive breast cancer (IBC) survival rate by 13%. Despite the clinical importance of lymph node involvement, the role of extracellular matrix (ECM) remodeling in metastases is unknown. We hypothesize that the spatial dysregulation of the coll...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2024-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866124003716/type/journal_article |
| _version_ | 1797226933264580608 |
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| author | Taylor S Hulahan Yeonhee Park Laura Spruill Hari Nakshatri Marvella Ford Peggi M Angel |
| author_facet | Taylor S Hulahan Yeonhee Park Laura Spruill Hari Nakshatri Marvella Ford Peggi M Angel |
| author_sort | Taylor S Hulahan |
| collection | DOAJ |
| description | OBJECTIVES/GOALS: Metastasis to regional areas decreases invasive breast cancer (IBC) survival rate by 13%. Despite the clinical importance of lymph node involvement, the role of extracellular matrix (ECM) remodeling in metastases is unknown. We hypothesize that the spatial dysregulation of the collagen proteome facilitates pro-tumorigenic immune infiltration. METHODS/STUDY POPULATION: Lymph node metastases were compared to patient-matched primary tumor and normal lymph nodes using tissue microarrays (TMA) from 31 generational South Carolina women with IBC (black women, BW n=10, white women, WW n=21) and lumpectomies from 5 triple-negative breast cancer (TNBC) patients (BW n=3; WW n=2) by ECM-targeted mass spectrometry imaging. RESULTS/ANTICIPATED RESULTS: Between metastatic and normal lymph nodes, 10% of peptides, primarily from fibrillar collagens, were significantly different by area under the receiver operating curve (AUROC>70%; p-value< 0.01) within the TMAs. In a subsequent preliminary study of the TNBC metastatic niche, a segmentation analysis of 152 putatively identified peptides and 117,909 pixels revealed 10 uniquely localized proteomic groups. 12 peptides were found to have significantly decreased relative peak intensities in lymph node metastases compared to the primary tumor and normal lymph nodes by a one-way ANOVA test (p< 0.05). 7 peptides could discriminate between metastatic and normal lymph nodes, while 22 peptides could discriminate between metastatic lymph nodes and the primary tumor (AUROC>0.70; p-value < 0.05). DISCUSSION/SIGNIFICANCE: Our preliminary interrogation highlights emerging differences between lymph node metastases, the primary tumor, and normal lymph nodes. Future work is needed to connect these discrete ECM proteomes to immune infiltration alterations, which could contribute to disparate patient outcomes. |
| first_indexed | 2024-04-24T14:32:46Z |
| format | Article |
| id | doaj.art-f0be0defa4b7442c8e3f8be136d88b92 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-24T14:32:46Z |
| publishDate | 2024-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-f0be0defa4b7442c8e3f8be136d88b922024-04-03T02:00:06ZengCambridge University PressJournal of Clinical and Translational Science2059-86612024-04-01812812810.1017/cts.2024.371429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry ImagingTaylor S Hulahan0Yeonhee Park1Laura Spruill2Hari Nakshatri3Marvella Ford4Peggi M Angel5Medical University of South CarolinaUniversity of Wisconsin-MadisonMedical University of South CarolinaUniversity of IndianaMedical University of South CarolinaMedical University of South CarolinaOBJECTIVES/GOALS: Metastasis to regional areas decreases invasive breast cancer (IBC) survival rate by 13%. Despite the clinical importance of lymph node involvement, the role of extracellular matrix (ECM) remodeling in metastases is unknown. We hypothesize that the spatial dysregulation of the collagen proteome facilitates pro-tumorigenic immune infiltration. METHODS/STUDY POPULATION: Lymph node metastases were compared to patient-matched primary tumor and normal lymph nodes using tissue microarrays (TMA) from 31 generational South Carolina women with IBC (black women, BW n=10, white women, WW n=21) and lumpectomies from 5 triple-negative breast cancer (TNBC) patients (BW n=3; WW n=2) by ECM-targeted mass spectrometry imaging. RESULTS/ANTICIPATED RESULTS: Between metastatic and normal lymph nodes, 10% of peptides, primarily from fibrillar collagens, were significantly different by area under the receiver operating curve (AUROC>70%; p-value< 0.01) within the TMAs. In a subsequent preliminary study of the TNBC metastatic niche, a segmentation analysis of 152 putatively identified peptides and 117,909 pixels revealed 10 uniquely localized proteomic groups. 12 peptides were found to have significantly decreased relative peak intensities in lymph node metastases compared to the primary tumor and normal lymph nodes by a one-way ANOVA test (p< 0.05). 7 peptides could discriminate between metastatic and normal lymph nodes, while 22 peptides could discriminate between metastatic lymph nodes and the primary tumor (AUROC>0.70; p-value < 0.05). DISCUSSION/SIGNIFICANCE: Our preliminary interrogation highlights emerging differences between lymph node metastases, the primary tumor, and normal lymph nodes. Future work is needed to connect these discrete ECM proteomes to immune infiltration alterations, which could contribute to disparate patient outcomes.https://www.cambridge.org/core/product/identifier/S2059866124003716/type/journal_article |
| spellingShingle | Taylor S Hulahan Yeonhee Park Laura Spruill Hari Nakshatri Marvella Ford Peggi M Angel 429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry Imaging Journal of Clinical and Translational Science |
| title | 429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry Imaging |
| title_full | 429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry Imaging |
| title_fullStr | 429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry Imaging |
| title_full_unstemmed | 429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry Imaging |
| title_short | 429 Spatial Investigation of the Extracellular Matrix Metastatic Niche in Invasive Breast Cancer by Mass Spectrometry Imaging |
| title_sort | 429 spatial investigation of the extracellular matrix metastatic niche in invasive breast cancer by mass spectrometry imaging |
| url | https://www.cambridge.org/core/product/identifier/S2059866124003716/type/journal_article |
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