过表达CD2/CD27可以抑制氮代谢途径的激活，并抑制巨噬细胞的M2极化，从而预防乳腺癌的脑转移。
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.
发表日期：2023 Sep 02
作者：
Guanyou Huang, Yujuan Wu, Hongchuan Gan, Liangzhao Chu
来源：
Brain Structure & Function
摘要：
我们的研究旨在通过TCGA（癌症基因组图谱）和SRA（序列读档文档）数据库，揭示CD2和CD27对乳腺癌（BC）脑转移肿瘤微环境的可能分子机制。我们从TCGA-BRCA数据集中计算了1222个BC样本的肿瘤浸润免疫细胞的比例以及免疫和间质细胞得分，并鉴定了候选过表达基因（DEGs）。我们进一步在SRA数据库的BC脑转移数据集SUB12911144中筛选了与BC脑转移相关的DEGs。最终，我们建立了一个小鼠乳腺癌脑转移模型进行体内验证。我们进一步筛选出了两个免疫调控的DEGs（CD2和CD27）。GSEA分析显示，CD2和CD27表达的下调与氮代谢通路的激活密切相关。CIBERSORT算法分析显示，肿瘤浸润免疫细胞的16种类型与CD2的表达和19种类型与CD27的表达有相关性。此外，CD2和CD27的表达与M2巨噬细胞的比例呈负相关。体内实验结果表明，CD2/CD27的过表达可以抑制M2巨噬细胞的极化，抑制乳腺癌脑转移。在肿瘤微环境中，CD2/CD27的过表达抑制了氮代谢通路的激活，抑制了M2巨噬细胞的极化，从而预防了乳腺癌的脑转移。版权所有©2023年。由Elsevier Inc.出版。
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.Copyright © 2023. Published by Elsevier Inc.