In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes

ObjectiveCSF2RB is the common beta chain of the heterodimeric receptors for the cytokines, granulocyte–macrophage 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 prol...

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Main Authors: Raghad Alshelaiel, Abdulmohsen Alkushi, Lolwah Abdullah Alriyees, Abir Abdullah Alamro, Humidah Alanazi, Areej Alhareeri, Bader AlMuzzaini, Mamoon Rashid
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Bioinformatics
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Online Access:https://www.frontiersin.org/articles/10.3389/fbinf.2025.1606828/full
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author Raghad Alshelaiel
Abdulmohsen Alkushi
Abdulmohsen Alkushi
Lolwah Abdullah Alriyees
Lolwah Abdullah Alriyees
Abir Abdullah Alamro
Humidah Alanazi
Areej Alhareeri
Areej Alhareeri
Bader AlMuzzaini
Bader AlMuzzaini
Mamoon Rashid
Mamoon Rashid
author_facet Raghad Alshelaiel
Abdulmohsen Alkushi
Abdulmohsen Alkushi
Lolwah Abdullah Alriyees
Lolwah Abdullah Alriyees
Abir Abdullah Alamro
Humidah Alanazi
Areej Alhareeri
Areej Alhareeri
Bader AlMuzzaini
Bader AlMuzzaini
Mamoon Rashid
Mamoon Rashid
author_sort Raghad Alshelaiel
collection DOAJ
description ObjectiveCSF2RB is the common beta chain of the heterodimeric receptors for the cytokines, granulocyte–macrophage 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, CSF2RB is abnormally expressed in a variety of tumors, especially in leukemia. The implications of CSF2RB in breast cancer remain unclear and have not been widely studied.MethodsWe analyzed CSF2RB 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.ResultsOur in silico analyses showed overexpression of CSF2RB in acute myeloid leukemia (AML) and decreased expression in breast invasive carcinoma (BRCA) compared to matched normal samples. Promoter methylation of CSF2RB was elevated in BRCA samples compared to normal samples. Our analysis further demonstrates that the CSF2RB 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+ T-cell infiltration levels that are positively correlated with the CSF2RB gene expression level. Wild-type CSF2RB shows higher expression than the mutated CSF2RB in breast cancer. CSF2RB expression (and/or mutation) has no significant effect on the overall survival probability. CSF2RB expression is downregulated in luminal and HER2-positive samples but upregulated in triple-negative breast cancer (TNBC), compared to that in normal samples.ConclusionThe results suggest a diverse role for the CSF2RB gene across different subtypes of breast cancer. To attribute a clear role to CSF2RB in breast cancer, further functional studies focusing on differential gene expression, methylation, and their prognostic effect in each breast cancer subtype are required.
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spelling doaj-art-dd7075b2e7cc4c23b640c65073f013c52025-08-20T03:23:30ZengFrontiers Media S.A.Frontiers in Bioinformatics2673-76472025-08-01510.3389/fbinf.2025.16068281606828In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypesRaghad Alshelaiel0Abdulmohsen Alkushi1Abdulmohsen Alkushi2Lolwah Abdullah Alriyees3Lolwah Abdullah Alriyees4Abir Abdullah Alamro5Humidah Alanazi6Areej Alhareeri7Areej Alhareeri8Bader AlMuzzaini9Bader AlMuzzaini10Mamoon Rashid11Mamoon Rashid12Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaCollege of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaKing Abdullah International Medical Research Center, Riyadh, Saudi ArabiaKing Abdullah International Medical Research Center, Riyadh, Saudi ArabiaDepartment of Surgery, King Abdulaziz Medical City, MNGHA, Riyadh, Saudi ArabiaDepartment of Biochemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaDepartment of Biochemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaKing Abdullah International Medical Research Center, Riyadh, Saudi ArabiaClinical Laboratory Sciences Department, College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaDepartment of Medical Genomics, King Abdullah International Medical Research Center, Riyadh, Saudi ArabiaKing Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaKing Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaDepartment of AI and Bioinformatics, King Abdullah International Medical Research Center, Riyadh, Saudi ArabiaObjectiveCSF2RB is the common beta chain of the heterodimeric receptors for the cytokines, granulocyte–macrophage 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, CSF2RB is abnormally expressed in a variety of tumors, especially in leukemia. The implications of CSF2RB in breast cancer remain unclear and have not been widely studied.MethodsWe analyzed CSF2RB 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.ResultsOur in silico analyses showed overexpression of CSF2RB in acute myeloid leukemia (AML) and decreased expression in breast invasive carcinoma (BRCA) compared to matched normal samples. Promoter methylation of CSF2RB was elevated in BRCA samples compared to normal samples. Our analysis further demonstrates that the CSF2RB 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+ T-cell infiltration levels that are positively correlated with the CSF2RB gene expression level. Wild-type CSF2RB shows higher expression than the mutated CSF2RB in breast cancer. CSF2RB expression (and/or mutation) has no significant effect on the overall survival probability. CSF2RB expression is downregulated in luminal and HER2-positive samples but upregulated in triple-negative breast cancer (TNBC), compared to that in normal samples.ConclusionThe results suggest a diverse role for the CSF2RB gene across different subtypes of breast cancer. To attribute a clear role to CSF2RB in breast cancer, further functional studies focusing on differential gene expression, methylation, and their prognostic effect in each breast cancer subtype are required.https://www.frontiersin.org/articles/10.3389/fbinf.2025.1606828/fullcancerbreast cancercolony-stimulating factor 2 receptor subunit betaprognosiscancer genomicsbioinformatics
spellingShingle Raghad Alshelaiel
Abdulmohsen Alkushi
Abdulmohsen Alkushi
Lolwah Abdullah Alriyees
Lolwah Abdullah Alriyees
Abir Abdullah Alamro
Humidah Alanazi
Areej Alhareeri
Areej Alhareeri
Bader AlMuzzaini
Bader AlMuzzaini
Mamoon Rashid
Mamoon Rashid
In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes
Frontiers in Bioinformatics
cancer
breast cancer
colony-stimulating factor 2 receptor subunit beta
prognosis
cancer genomics
bioinformatics
title In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes
title_full In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes
title_fullStr In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes
title_full_unstemmed In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes
title_short In silico analysis of CSF2RB from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes
title_sort in silico analysis of csf2rb from cancer genomic databases reveals a heterogeneous role in different breast cancer subtypes
topic cancer
breast cancer
colony-stimulating factor 2 receptor subunit beta
prognosis
cancer genomics
bioinformatics
url https://www.frontiersin.org/articles/10.3389/fbinf.2025.1606828/full
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