Department of Breast Surgery, the First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
BMC Cancer. 2023 May 15;23(1):440. doi: 10.1186/s12885-023-10904-4.
Current studies on the role of ARHGAP39 mainly focused on its effect on neurodevelopment. However, there are few studies on the comprehensive analysis of ARHGAP39 in breast cancer.
ARHGAP39 expression level was analyzed based on the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression Project (GTEx), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database and validated by qPCR in various cell lines and tumor tissues. The prognostic value was analyzed using Kaplan-Meier curve analysis. CCK-8 and transwell assays were conducted to identify the biological function of ARHGAP39 in tumorigenesis. Signaling pathways related to ARHGAP39 expression were identified by the GO and KEGG enrichment analysis and gene set enrichment analysis (GSEA). The correlations between ARHGAP39 and cancer immune infiltrates were investigated via TIMER, CIBERSORT, ESTIMATE and tumor-immune system interactions database (TISIDB).
ARHGAP39 was overexpressed in breast cancer and associated with poor survival outcomes. In vitro experiments revealed that ARHGAP39 could facilitate the proliferation, migration, and invasion capability of breast cancer cells. GSEA analysis showed that the main enrichment pathways of ARHGAP39 was immunity-related pathways. Considering the immune infiltration level, ARHGAP39 was negatively associated with infiltrating levels of CD8 + T cell and macrophage, and positively associated with CD4 + T cell. Furthermore, ARHGAP39 was significantly negatively correlated with immune score, stromal score, and ESTIMATE score.
Our findings suggested that ARHGAP39 can be used as a potential therapeutic target and prognostic biomarker in breast cancer. ARHGAP39 was indeed a determinant factor of immune infiltration.
目前关于 ARHGAP39 作用的研究主要集中在其对神经发育的影响上。然而，关于 ARHGAP39 在乳腺癌中的综合分析研究较少。
基于癌症基因组图谱（TCGA）、基因型组织表达计划（GTEx）和临床蛋白质组肿瘤分析联盟（CPTAC）数据库分析 ARHGAP39 的表达水平，并在各种细胞系和肿瘤组织中通过 qPCR 进行验证。通过 Kaplan-Meier 曲线分析评估预后价值。通过 CCK-8 和 Transwell 测定鉴定 ARHGAP39 在肿瘤发生中的生物学功能。通过 GO 和 KEGG 富集分析和基因集富集分析（GSEA）鉴定与 ARHGAP39 表达相关的信号通路。通过 TIMER、CIBERSORT、ESTIMATE 和肿瘤免疫系统相互作用数据库（TISIDB）研究 ARHGAP39 与癌症免疫浸润的相关性。
ARHGAP39 在乳腺癌中过度表达，并与不良生存结局相关。体外实验表明，ARHGAP39 可促进乳腺癌细胞的增殖、迁移和侵袭能力。GSEA 分析表明，ARHGAP39 的主要富集途径是免疫相关途径。考虑到免疫浸润水平，ARHGAP39 与 CD8+T 细胞和巨噬细胞的浸润水平呈负相关，与 CD4+T 细胞呈正相关。此外，ARHGAP39 与免疫评分、基质评分和 ESTIMATE 评分显著负相关。
我们的研究结果表明，ARHGAP39 可作为乳腺癌潜在的治疗靶点和预后生物标志物。ARHGAP39 确实是免疫浸润的决定因素。
