Frontiers in immunology · 2025
Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages.
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Ko Tun Kiat, Guo Zexi, Kannan Bavani, Lim Boon Yee, Lee Jing Yi, Li Zhimei, Lee Elizabeth Chun Yong, Teh Bin Tean, Chan Jason Yongsheng
Аннотация
INTRODUCTION: Recent 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.
METHODS: We 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.
RESULTS: Majority 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.
DISCUSSION: In 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.
METHODS: We 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.
RESULTS: Majority 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.
DISCUSSION: In 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.