Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages
IntroductionRecent epidemiological data suggests a rising incidence of breast angiosarcoma (AS-B) in the Western population, with over two-thirds related to irradiation or chronic lymphedema. However, unlike head and neck angiosarcoma (AS-HN), AS-B disease characteristics in Asia remain unclear.Meth...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1515935/full |
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| author | Tun Kiat Ko Zexi Guo Bavani Kannan Boon Yee Lim Jing Yi Lee Zhimei Li Elizabeth Chun Yong Lee Bin Tean Teh Bin Tean Teh Jason Yongsheng Chan Jason Yongsheng Chan Jason Yongsheng Chan |
| author_facet | Tun Kiat Ko Zexi Guo Bavani Kannan Boon Yee Lim Jing Yi Lee Zhimei Li Elizabeth Chun Yong Lee Bin Tean Teh Bin Tean Teh Jason Yongsheng Chan Jason Yongsheng Chan Jason Yongsheng Chan |
| author_sort | Tun Kiat Ko |
| collection | DOAJ |
| description | IntroductionRecent epidemiological data suggests a rising incidence of breast angiosarcoma (AS-B) in the Western population, with over two-thirds related to irradiation or chronic lymphedema. However, unlike head and neck angiosarcoma (AS-HN), AS-B disease characteristics in Asia remain unclear.MethodsWe examined clinical patterns of angiosarcoma patients (n = 176) seen in an Asiantertiary cancer center from 1999 to 2021, and specifically investigated the molecular and immune features of AS-B in comparison to AS-HN. Data from whole genome sequencing (WGS), NanoString gene expression profiling and 10x Genomics Visium spatial transcriptomics were analyzed.ResultsMajority of cases were AS-HN (n = 104; 59.1%), while AS-B (n = 16, all females) accounted for 9.1% of the cases. The median age at diagnosis was 43 years (range, 26 to 74). Based on WGS, 4 of the 7 AS-B had non-synonymous somatic variants in 47 genes (range, 2 to 28 per case). These genes were functionally annotated and were enriched in cancer-related pathways such as regulation of cell differentiation, VEGFR and receptor tyrosine kinases signaling pathways. By NanoString gene expression profiling, ASB, compared to AS-HN, were enriched for angiogenesis, notch signaling and metastasis-associated matrix remodeling pathways. Additionally, AS-B were enriched for macrophages and CD8+ T cells expression signatures. Similarly, Visium spatial transcriptomics showed that AS-B were enriched for macrophages and T-cells.DiscussionIn conclusion, in our AS-B cases, we observed a convergence of both mutational and expression signatures on angiogenic-related pathways. Thus, anti-angiogenic therapy could be an option to treat AS-B. |
| format | Article |
| id | doaj-art-0a82b2df19d6491bb77a1550b663796c |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-0a82b2df19d6491bb77a1550b663796c2025-01-13T06:11:02ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.15159351515935Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophagesTun Kiat Ko0Zexi Guo1Bavani Kannan2Boon Yee Lim3Jing Yi Lee4Zhimei Li5Elizabeth Chun Yong Lee6Bin Tean Teh7Bin Tean Teh8Jason Yongsheng Chan9Jason Yongsheng Chan10Jason Yongsheng Chan11Cancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeCancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeCancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeCancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeCancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeCancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeCancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeLaboratory of Cancer Epigenome, National Cancer Centre Singapore, Singapore, SingaporeOncology Academic Clinical Program, Duke-NUS Medical School, Singapore, SingaporeCancer Discovery Hub, National Cancer Centre Singapore, Singapore, SingaporeOncology Academic Clinical Program, Duke-NUS Medical School, Singapore, SingaporeDivision of Medical Oncology, National Cancer Centre Singapore, Singapore, SingaporeIntroductionRecent epidemiological data suggests a rising incidence of breast angiosarcoma (AS-B) in the Western population, with over two-thirds related to irradiation or chronic lymphedema. However, unlike head and neck angiosarcoma (AS-HN), AS-B disease characteristics in Asia remain unclear.MethodsWe examined clinical patterns of angiosarcoma patients (n = 176) seen in an Asiantertiary cancer center from 1999 to 2021, and specifically investigated the molecular and immune features of AS-B in comparison to AS-HN. Data from whole genome sequencing (WGS), NanoString gene expression profiling and 10x Genomics Visium spatial transcriptomics were analyzed.ResultsMajority of cases were AS-HN (n = 104; 59.1%), while AS-B (n = 16, all females) accounted for 9.1% of the cases. The median age at diagnosis was 43 years (range, 26 to 74). Based on WGS, 4 of the 7 AS-B had non-synonymous somatic variants in 47 genes (range, 2 to 28 per case). These genes were functionally annotated and were enriched in cancer-related pathways such as regulation of cell differentiation, VEGFR and receptor tyrosine kinases signaling pathways. By NanoString gene expression profiling, ASB, compared to AS-HN, were enriched for angiogenesis, notch signaling and metastasis-associated matrix remodeling pathways. Additionally, AS-B were enriched for macrophages and CD8+ T cells expression signatures. Similarly, Visium spatial transcriptomics showed that AS-B were enriched for macrophages and T-cells.DiscussionIn conclusion, in our AS-B cases, we observed a convergence of both mutational and expression signatures on angiogenic-related pathways. Thus, anti-angiogenic therapy could be an option to treat AS-B.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1515935/fullsarcomanext generation sequencingimmunotherapytumor-infiltrating macrophagesimmune-oncology |
| spellingShingle | Tun Kiat Ko Zexi Guo Bavani Kannan Boon Yee Lim Jing Yi Lee Zhimei Li Elizabeth Chun Yong Lee Bin Tean Teh Bin Tean Teh Jason Yongsheng Chan Jason Yongsheng Chan Jason Yongsheng Chan Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages Frontiers in Immunology sarcoma next generation sequencing immunotherapy tumor-infiltrating macrophages immune-oncology |
| title | Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages |
| title_full | Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages |
| title_fullStr | Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages |
| title_full_unstemmed | Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages |
| title_short | Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages |
| title_sort | multiomics characterization of breast angiosarcoma from an asian cohort reveals enrichment for angiogenesis signaling pathway and tumor infiltrating macrophages |
| topic | sarcoma next generation sequencing immunotherapy tumor-infiltrating macrophages immune-oncology |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1515935/full |
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