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

Objective: 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, is abnormally expressed in a variety of tumors, especially in leukemia. The implications of in breast cancer remain unclear and have not been widely studied.

Methods: We analyzed 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.

Results: Our analyses showed overexpression of in acute myeloid leukemia (AML) and decreased expression in breast invasive carcinoma (BRCA) compared to matched normal samples. Promoter methylation of was elevated in BRCA samples compared to normal samples. Our analysis further demonstrates that the 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 gene expression level. Wild-type shows higher expression than the mutated in breast cancer. expression (and/or mutation) has no significant effect on the overall survival probability. expression is downregulated in luminal and HER2-positive samples but upregulated in triple-negative breast cancer (TNBC), compared to that in normal samples.

Conclusion: The results suggest a diverse role for the gene across different subtypes of breast cancer. To attribute a clear role to in breast cancer, further functional studies focusing on differential gene expression, methylation, and their prognostic effect in each breast cancer subtype are required.