Triple-Negative Breast Cancer with High Levels of Annexin A1 Expression Is Associated with Mast Cell Infiltration, Inflammation, and Angiogenesis

International Journal of Molecular Sciences

Li Yan¹  Toru Ohtake¹  Eriko Katsuta²  Masanori Oshi²  Maiko Okano²  AliLinsk Butash²  Koji Kono³  Xuan Peng³  Kazunoshin Tachibana⁴  Katsuharu Saito⁵  Hirokazu Okayama⁵  Kazuaki Takabe⁵ 

[1] Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;Breast Surgery, Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;;Department of Biostatistics &Department of Breast Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan;Department of Gastrointestinal Tract Surgery, Fukushima Medical University School of Medicine, Fukushima 960-1295, Japan;

关键词: breast cancer;    ANXA1;    mast cell;    inflammation;    TNBC;    CIBERSORT;    GSEA;   

DOI  :  10.3390/ijms20174197

来源: DOAJ

【 摘 要 】

Annexin A1 (ANXA1) is a phospholipid-linked protein involved in inflammation, immune response, and mast cell reactivity. Recently, we reported that ANXA1 is associated with aggressive features of triple-negative breast cancer (TNBC); however, its clinical relevance remains controversial. We hypothesized that human TNBC with high expression of ANXA1 mRNA is associated with pro-cancerous immune cell infiltration, including mast cells, and with an aggressive phenotype. Clinical and RNA-seq data were obtained from The Cancer Genome Atlas (TCGA, n = 1079) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (n = 1904). TNBC patients had significantly higher levels of ANXA1 expression compared to the other subtypes in both TCGA and METABRIC cohorts (p < 0.001). ANXA1 protein expression was assessed by immunohistochemistry in Japanese TNBC patient cohort (n = 48), where 17 cases (35.4%) had positive ANXA1 staining, and their overall survival was significantly shorter compared with negative staining group (p = 0.008). The CIBERSORT algorithm was used to calculate immune cell infiltrations. ANXA1 high tumors were associated with activated mast cells and M2 macrophages (p > 0.01), but did not show any association with tumor heterogeneity nor cytolytic activity. High expression of ANXA1 group enriched inflammation, epithelial-to-mesenchymal transition (EMT), and angiogenesis-related genes in a gene set enrichment assay in both cohorts. To our knowledge, this is the first study to demonstrate that ANXA1 is associated with infiltration of mast cells and inflammation that is associated with the aggressive phenotype of TNBC, such as EMT and angiogenesis.

【 授权许可】

Unknown