{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:46:27Z","timestamp":1788522387208,"version":"build-2803163510"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T00:00:00Z","timestamp":1680048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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 \u201cbiological processes\u201d (BP), including \u201corganelle fission\u201d and \u201cnuclear division\u201d. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis demonstrated that these DEGs from two datasets were both significantly enriched in the \u201ccell cycle\u201d. Common hub genes between the DEGs in GSE7390 and GSE21653 were negatively associated with RAI2 expression, including CCNA2, MAD2L1, MELK, CDC20, and CCNB2.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2023.1134149","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T05:13:04Z","timestamp":1680066784000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Comprehensive analysis of the expression and prognosis for RAI2: A promising biomarker in breast 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