Comprehensive Analysis Of<i> Gjb1</I> in Breast Cancer: Its Implications in Survival and Molecular Mechanisms

Abstract

Background/Aim: Breast cancer is the leading cause of cancer-related mortality among women worldwide. The connexin (Cx) family, including GJB1 (Cx32), plays complex roles in tumor progression depending on cellular context and cancer subtype. While Cx32 overexpression has been linked to lymph node metastasis, its effects on survival and molecular processes remain unclear. Herein, we aimed to investigate the role of GJB1 in breast cancer by examining its impact on survival and cellular processes in addition to its expression pattern in tumor subtypes, using public datasets. Materials and Methods: We conducted a comprehensive analysis of GJB1 in breast cancer using METABRIC patient dataset, Cancer Cell Line Encylopedia, and other publicly available databases. We examined the association between GJB1 expression and patient survival, performed differential gene expression analysis, and explored gene set enrichment to identify biological processes associated with high GJB1 expression. Results: GJB1 was significantly down-regulated in breast cancer tissues compared to normal tissues. However, patients with high GJB1 expression had significantly poorer survival compared to those with low expression, with the median survival reduced by over 25 months. Gene ontology (GO) analysis revealed that down- regulated genes in the GJB1-high group were enriched in extracellular matrix components and membrane junctions, while up-regulated genes were associated with mitochondrial function and cellular respiration. Conclusion: Our findings suggest a dual role for GJB1 in breast cancer. Although it is generally down-regulated, high GJB1 expression is associated with poorer survival, implying a potential oncogenic role. Further studies are needed to clarify the role of GJB1 in breast cancer and explore its therapeutic implications.