GSK-3β Regulates Tumor Stemness and Immune-Related Pathways in Triple-Negative Breast Cancer: A Bioinformatics and Experimental Validation Study.
Given the crucial roles of GSK-3β in epithelial-mesenchymal transition (EMT), we assume that it may also be involved in tumor stemness, immune evasion, and drug resistance in triple-negative breast cancer (TNBC). This study was designed to analyze the expression and clinical significance of GSK-3β and investigate its association with tumor stemness-related and immune-related genes.
GSK-3β expression and clinical data of TNBC patients were obtained from TCGA. Survival analysis, differential gene expression, and gene set enrichment analysis (GSEA) were performed to explore associations between GSK-3β and tumor stemness, immune response, and clinical outcomes in TNBC. Immune cell infiltration was assessed using xCell, and key GSK-3β-related proteins were validated via parallel reaction monitoring-based proteomics.
GSK-3β expression was significantly upregulated in TNBC and was associated with poorer overall survival. In TNBC, 24 GSK-3β-associated genes linked to tumor stemness and immune response were identified, all of which were downregulated in the high GSK-3β expression group. Proteomic analysis further validated differential expression of key proteins, including upregulation of SERPINB2, KIT, and NOTCH1 and downregulation of DNMT1, MAPK1, and EP300 in GSK-3β-overexpressing cells.
GSK-3β overexpression was associated with poor prognosis and was found to influence tumor stemness, immune modulation, and key signaling pathways that drive tumor progression and therapeutic resistance.
GSK-3β expression and clinical data of TNBC patients were obtained from TCGA. Survival analysis, differential gene expression, and gene set enrichment analysis (GSEA) were performed to explore associations between GSK-3β and tumor stemness, immune response, and clinical outcomes in TNBC. Immune cell infiltration was assessed using xCell, and key GSK-3β-related proteins were validated via parallel reaction monitoring-based proteomics.
GSK-3β expression was significantly upregulated in TNBC and was associated with poorer overall survival. In TNBC, 24 GSK-3β-associated genes linked to tumor stemness and immune response were identified, all of which were downregulated in the high GSK-3β expression group. Proteomic analysis further validated differential expression of key proteins, including upregulation of SERPINB2, KIT, and NOTCH1 and downregulation of DNMT1, MAPK1, and EP300 in GSK-3β-overexpressing cells.
GSK-3β overexpression was associated with poor prognosis and was found to influence tumor stemness, immune modulation, and key signaling pathways that drive tumor progression and therapeutic resistance.
Authors
Zhou Zhou, Wang Wang, Zhu Zhu, Chen Chen, Bai Bai, Hu Hu, Wang Wang, Qi Qi, Yin Yin, Sun Sun
View on Pubmed