Overexpression of CD2/CD27 could inhibit the activation of nitrogen metabolism pathways and suppress M2 polarization of macrophages, thereby preventing brain metastasis of breast cancer

• Published in: Translational oncology Vol. 37; p. 101768
• Main Authors: Huang, Guanyou, Wu, Yujuan, Gan, Hongchuan, Chu, Liangzhao
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-11-2023; Neoplasia Press; Elsevier
• Subjects: Brain metastasis; Breast cancer; CD2; CD27; Macrophage polarization; Nitrogen metabolic pathway; Original Research; CD2; BC; TAM; DEGs; BCS; Macrophage polarization; Brain metastasis; PPI; CD27; Breast cancer; Nitrogen metabolic pathway; TME
• ISSN: 1936-5233; 1936-5233
• DOI: 10.1016/j.tranon.2023.101768

•CD2 and CD27 are the core immune genes involved in brain metastases of BC.•CD2 and CD27 expression are closely associated with brain metastases of BC.•Reduced CD2 and CD27 are related to the activation of nitrogen metabolic pathways.•CD2 and CD27 show a negative correlation with the proportion of M2 macrophages.•Our study identifies potential therapeutic targets for brain metastases of BC.
Our study aimed to reveal the possible molecular mechanisms of CD2 and CD27 in influencing the tumor microenvironment of breast cancer (BC) brain metastasis based on the TCGA (The Cancer Genome Atlas) and SRA (Sequence Read Archive) databases.
We calculated the proportions of tumor-infiltrating immune cells and the immune and stromal cell scores in 1222 BC samples from the TCGA-BRCA dataset, followed by identification of candidate DEGs. We further screened for BC brain metastasis-related DEGs in the BC brain metastasis dataset SUB12911144 from the SRA database. Finally, we established a mouse breast cancer brain metastasis model for in vivo validation.
We further screened two immune-regulatory DEGs (CD2 and CD27). GSEA analysis showed that the downregulation of CD2 and CD27 expression was closely related to the activation of nitrogen metabolism pathways. CIBERSORT algorithm analysis showed a correlation between the expression of 16 types of tumor-infiltrating immune cells and CD2 and 19 types of tumor-infiltrating immune cells and CD27. In addition, CD2 and CD27 expression were negatively associated with the proportion of M2 macrophages. In vivo experimental results demonstrated that overexpression of CD2/CD27 could suppress the M2 polarization of macrophages and inhibit breast cancer brain metastasis.
In the tumor microenvironment, overexpression of CD2/CD27 inhibited the activation of nitrogen metabolism pathways and suppressed M2 polarization of macrophages, thereby preventing brain metastasis of breast cancer.