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Bioinform."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p><jats:italic>CSF2RB<\/jats:italic> is the common beta chain of the heterodimeric receptors for the cytokines, granulocyte\u2013macrophage colony-stimulating factor (GM-CSF), interleukin 3 (IL-3), and interleukin 5 (IL-5). The activation of these cell surface receptors results in functional responses including cellular proliferation, differentiation, survival, and maturation via multiple signaling pathways such as JAK2\/STAT5, MAPK, and PI3-kinase\/AKT. Moreover, <jats:italic>CSF2RB<\/jats:italic> is abnormally expressed in a variety of tumors, especially in leukemia. The implications of <jats:italic>CSF2RB<\/jats:italic> in breast cancer remain unclear and have not been widely studied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analyzed <jats:italic>CSF2RB<\/jats:italic> genetic changes, mRNA expression, DNA methylation, prognosis, and immune infiltration levels across different tumor types, with a focus on breast and hematological malignancies. The data used in this study were obtained from publicly available cancer genomics databases, such as TCGA, cBioPortal, TIMER2.0, GEPIA, and UALCAN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our <jats:italic>in silico<\/jats:italic> analyses showed overexpression of <jats:italic>CSF2RB<\/jats:italic> in acute myeloid leukemia (AML) and decreased expression in breast invasive carcinoma (BRCA) compared to matched normal samples. Promoter methylation of <jats:italic>CSF2RB<\/jats:italic> was elevated in BRCA samples compared to normal samples. Our analysis further demonstrates that the <jats:italic>CSF2RB<\/jats:italic> gene has a favorable prognostic effect in BRCA, although this was not statistically significant across all databases studied. We found that BRCA and its subtypes exhibit high CD8<jats:sup>+<\/jats:sup> T-cell infiltration levels that are positively correlated with the <jats:italic>CSF2RB<\/jats:italic> gene expression level. Wild-type <jats:italic>CSF2RB<\/jats:italic> shows higher expression than the mutated <jats:italic>CSF2RB<\/jats:italic> in breast cancer. <jats:italic>CSF2RB<\/jats:italic> expression (and\/or mutation) has no significant effect on the overall survival probability. <jats:italic>CSF2RB<\/jats:italic> expression is downregulated in luminal and HER2-positive samples but upregulated in triple-negative breast cancer (TNBC), compared to that in normal samples.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The results suggest a diverse role for the <jats:italic>CSF2RB<\/jats:italic> gene across different subtypes of breast cancer. To attribute a clear role to <jats:italic>CSF2RB<\/jats:italic> in breast cancer, further functional studies focusing on differential gene expression, methylation, and their prognostic effect in each breast cancer subtype are required.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fbinf.2025.1606828","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T05:25:23Z","timestamp":1754371523000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes"],"prefix":"10.3389","volume":"5","author":[{"given":"Raghad","family":"Alshelaiel","sequence":"first","affiliation":[]},{"given":"Abdulmohsen","family":"Alkushi","sequence":"additional","affiliation":[]},{"given":"Lolwah Abdullah","family":"Alriyees","sequence":"additional","affiliation":[]},{"given":"Abir Abdullah","family":"Alamro","sequence":"additional","affiliation":[]},{"given":"Humidah","family":"Alanazi","sequence":"additional","affiliation":[]},{"given":"Areej","family":"Alhareeri","sequence":"additional","affiliation":[]},{"given":"Bader","family":"AlMuzzaini","sequence":"additional","affiliation":[]},{"given":"Mamoon","family":"Rashid","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2566","DOI":"10.1158\/0008-5472.can-14-2946","article-title":"G-CSF promotes neuroblastoma tumorigenicity and metastasis via STAT3-Dependent cancer stem cell activation","volume":"75","author":"Agarwal","year":"2015","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.breast.2022.08.010","article-title":"Current and future burden of breast cancer: global statistics for 2020 and 2040","volume":"66","author":"Arnold","year":"2022","journal-title":"Breast"},{"key":"B3","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/s41375-021-01462-4","article-title":"The IL-3, IL-5, and GM-CSF common receptor beta chain mediates oncogenic activity of FLT3-ITD-positive AML","volume":"36","author":"Charlet","year":"2022","journal-title":"Leukemia"},{"key":"B4","doi-asserted-by":"publisher","first-page":"631650","DOI":"10.3389\/fcvm.2021.631650","article-title":"Integrated DNA methylation and gene expression analysis identified S100A8 and S100A9 in the pathogenesis of obesity","volume":"8","author":"Chen","year":"2021","journal-title":"Front. 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