Multiomics characterization of breast angiosarcoma from an Asian cohort reveals enrichment for angiogenesis signaling pathway and tumor-infiltrating macrophages

• Published in: Frontiers in immunology 2025-01, Vol.15, p.1515935
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Asian People - genetics; Breast Neoplasms - genetics; Breast Neoplasms - immunology; Breast Neoplasms - pathology; Cohort Studies; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Hemangiosarcoma - genetics; Hemangiosarcoma - metabolism; Hemangiosarcoma - pathology; Humans; immune-oncology; Immunology; immunotherapy; Middle Aged; Multiomics; Neovascularization, Pathologic - genetics; next generation sequencing; sarcoma; Signal Transduction; Transcriptome; Tumor Microenvironment - immunology; Tumor-Associated Macrophages - immunology; Tumor-Associated Macrophages - metabolism; tumor-infiltrating macrophages
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1515935

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. 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. 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. 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.