Alshelaiel Raghad, Alkushi Abdulmohsen, Alriyees Lolwah Abdullah, Alamro Abir Abdullah, Alanazi Humidah, Alhareeri Areej, AlMuzzaini Bader, Rashid Mamoon
Department of Biochemistry, College of Science, King Saud University, Riyadh, Saudi Arabia.
College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.
Front Bioinform. 2025 Aug 5;5:1606828. doi: 10.3389/fbinf.2025.1606828. eCollection 2025.
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.
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.
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.
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.
是细胞因子、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、白细胞介素3（IL-3）和白细胞介素5（IL-5）异二聚体受体的共同β链。这些细胞表面受体的激活通过多种信号通路，如JAK2/STAT5、MAPK和PI3-激酶/AKT，导致包括细胞增殖、分化、存活和成熟在内的功能反应。此外，在多种肿瘤中异常表达，尤其是在白血病中。在乳腺癌中的意义仍不清楚，尚未得到广泛研究。
我们分析了不同肿瘤类型中的基因变化、mRNA表达、DNA甲基化、预后和免疫浸润水平，重点是乳腺癌和血液系统恶性肿瘤。本研究中使用的数据来自公开可用的癌症基因组数据库，如TCGA、cBioPortal、TIMER2.0、GEPIA和UALCAN。
我们的分析显示，与匹配的正常样本相比，急性髓系白血病（AML）中表达上调，而乳腺浸润性癌（BRCA）中表达降低。与正常样本相比，BRCA样本中启动子甲基化水平升高。我们的分析进一步表明，该基因在BRCA中具有良好的预后作用，尽管在所有研究的数据库中这一结果无统计学意义。我们发现BRCA及其亚型表现出较高的CD8 T细胞浸润水平，且与基因表达水平呈正相关。野生型在乳腺癌中的表达高于突变型。表达（和/或突变）对总生存概率无显著影响。与正常样本相比，管腔型和HER2阳性样本中表达下调，但在三阴性乳腺癌（TNBC）中上调。
结果表明该基因在不同亚型乳腺癌中发挥多种作用。为明确该基因在乳腺癌中的作用，需要进一步针对各乳腺癌亚型的差异基因表达、甲基化及其预后作用进行功能研究。
