Dai Ji, Chen Qi, Li Guoqing, Chen Mengze, Sun Haohang, Yan Meidi
General Surgery I (Thyroid, Breast, Vascular, Hernia Surgery), People's Hospital of Zhenhai, Ningbo, China.
Front Oncol. 2022 Sep 21;12:965136. doi: 10.3389/fonc.2022.965136. eCollection 2022.
Brain metastasis is a primary cause of morbidity and mortality in breast cancer patients. Therefore, elucidation and understanding of the underlying mechanisms are essential for the development of new therapeutic strategies.
Differential gene analysis was performed for those with and without distant metastasis in The Cancer Genome Atlas (TCGA) database and those with and without recurrence in the brain in the dataset GSE12276. The differentially expressed genes procured from the two databases were intersected to obtain the intersecting genes associated with brain metastasis. Thereafter, the intersecting genes were subjected to LASSO model construction to screen for prognostic genes. The expression of the obtained genes in metastatic breast cancer was observed, and survival analysis was performed. Finally, GSEA analysis of the obtained genes was performed, and the relationship between them and immune cells was explored.
A total of 335 differential genes for the occurrence of distant metastases were obtained based on the TCGA database. A total of 1070 differential genes for recurrence to the brain were obtained based on the dataset GSE12276. The Venn diagram showed 24 intersecting genes associated with brain metastasis. The LASSO prognostic model contained a total of five genes (GBP2, GPR171, DIRAS3, RAC2, and CACNA1D). Expression difference analysis showed that GBP2, GPR171, DIRAS3, and RAC2 were significantly down-regulated in expression in metastatic breast cancer compared with primary breast cancer tumors. Only GPR171, DIRAS3, and RAC2 were strongly correlated with the overall survival of breast cancer patients. Their correlation analysis with immune cells showed that the correlation coefficient between the expression levels of DIRAS3 and immune cells was low, and the expression levels of GPR171 and RAC2 were more closely correlated with B cells and macrophages.
The expression of DIRAS3, GPR171 and RAC2, genes associated with brain metastasis, was reduced in metastatic breast cancer, and GPR171 was found to promote brain metastasis of breast cancer cells by inducing B cells and thereby.
脑转移是乳腺癌患者发病和死亡的主要原因。因此，阐明和理解其潜在机制对于开发新的治疗策略至关重要。
对癌症基因组图谱（TCGA）数据库中有无远处转移的患者以及数据集GSE12276中有无脑复发的患者进行差异基因分析。将从两个数据库中获得的差异表达基因进行交集分析，以获得与脑转移相关的交集基因。此后，对交集基因进行LASSO模型构建以筛选预后基因。观察所得基因在转移性乳腺癌中的表达，并进行生存分析。最后，对所得基因进行基因集富集分析（GSEA），并探讨它们与免疫细胞之间的关系。
基于TCGA数据库共获得335个与远处转移发生相关的差异基因。基于数据集GSE12276共获得1070个与脑复发相关的差异基因。维恩图显示有24个与脑转移相关的交集基因。LASSO预后模型共包含五个基因（GBP2、GPR171、DIRAS3、RAC2和CACNA1D）。表达差异分析表明，与原发性乳腺癌肿瘤相比，GBP2、GPR171、DIRAS3和RAC2在转移性乳腺癌中的表达显著下调。只有GPR171、DIRAS3和RAC2与乳腺癌患者的总生存期密切相关。它们与免疫细胞的相关性分析表明，DIRAS3表达水平与免疫细胞之间的相关系数较低，而GPR171和RAC2的表达水平与B细胞和巨噬细胞的相关性更强。
与脑转移相关的DIRAS3、GPR171和RAC2基因在转移性乳腺癌中的表达降低，并且发现GPR171通过诱导B细胞从而促进乳腺癌细胞的脑转移。
