Jiao Ying, Li Shiyu, Gong Juejun, Zheng Kun, Xie Ya
Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Institute of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK-Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.
Front Oncol. 2023 Mar 29;13:1134149. doi: 10.3389/fonc.2023.1134149. eCollection 2023.
Retinoic acid-induced 2 (RAI2) was initially related to cell differentiation and induced by retinoic acid. RAI2 has been identified as an emerging tumor suppressor in breast cancer and colorectal cancer.
In this study, we performed systematic analyses of RAI2 in breast cancer. Meta-analysis and Kaplan-Meier survival curves were applied to identify the survival prediction potential of RAI2. Moreover, the association between RAI2 expression and the abundance of six tumor-infiltrating immune cells was investigated by TIMER, including B cells, CD8+ T cells, CD4+ T cells, B cells, dendritic cells, neutrophils, and macrophages. The expression profiles of high and low RAI2 mRNA levels in GSE7390 were compared to identify differentially expressed genes (DEGs) and the biological function of these DEGs was analyzed by R software, which was further proved in GSE7390.
Our results showed that the normal tissues had more RAI2 expression than breast cancer tissues. Patients with high RAI2 expression were related to a favorable prognosis and more immune infiltrates. A total of 209 DEGs and 182 DEGs were identified between the expression profiles of high and low RAI2 mRNA levels in the GSE7390 and GSE21653 databases, respectively. Furthermore, Gene Ontology (GO) enrichment indicated that these DEGs from two datasets were both mainly distributed in "biological processes" (BP), including "organelle fission" and "nuclear division". Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis demonstrated that these DEGs from two datasets were both significantly enriched in the "cell cycle". Common hub genes between the DEGs in GSE7390 and GSE21653 were negatively associated with RAI2 expression, including CCNA2, MAD2L1, MELK, CDC20, and CCNB2.
These results above suggested that RAI2 might play a pivotal role in preventing the initiation and progression of breast cancer. The present study may contribute to understanding the molecular mechanisms of RAI2 and enriching biomarkers to predict patient prognosis in breast cancer.
维甲酸诱导蛋白2（RAI2）最初与细胞分化相关且由维甲酸诱导产生。RAI2已被确定为乳腺癌和结直肠癌中一种新兴的肿瘤抑制因子。
在本研究中，我们对乳腺癌中的RAI2进行了系统分析。应用荟萃分析和Kaplan-Meier生存曲线来确定RAI2的生存预测潜力。此外，通过TIMER研究了RAI2表达与六种肿瘤浸润免疫细胞丰度之间的关联，这六种免疫细胞包括B细胞、CD8 + T细胞、CD4 + T细胞、B细胞、树突状细胞、中性粒细胞和巨噬细胞。比较了GSE7390中RAI2 mRNA高表达水平和低表达水平的表达谱，以鉴定差异表达基因（DEG），并通过R软件分析这些DEG的生物学功能，这在GSE7390中得到了进一步验证。
我们的结果表明，正常组织中的RAI2表达高于乳腺癌组织。RAI2高表达的患者预后良好且免疫浸润更多。在GSE7390和GSE21653数据库中，RAI2 mRNA高表达水平和低表达水平的表达谱之间分别鉴定出209个和182个DEG。此外，基因本体（GO）富集表明，来自两个数据集的这些DEG主要分布在“生物过程”（BP）中，包括“细胞器分裂”和“核分裂”。京都基因与基因组百科全书（KEGG）通路分析表明，来自两个数据集的这些DEG均在“细胞周期”中显著富集。GSE7390和GSE21653中DEG之间的共同枢纽基因与RAI2表达呈负相关，包括CCNA2、MAD2L1、MELK、CDC20和CCNB2。
上述结果表明，RAI2可能在预防乳腺癌的发生和发展中起关键作用。本研究可能有助于理解RAI2的分子机制，并丰富预测乳腺癌患者预后的生物标志物。
