CCL18 and EGF May Serve as Potential Prognostic Biomarkers and Therapeutic Targets for Human Breast Cancer.

Abstract

Background: Breast cancer (BRCA) remains a leading cause of cancer-related mortality among women. CCL18 and EGF are implicated in tumor biology; however, their roles in BRCA remain partly defined. This study investigates their expression profiles, immune associations, prognostic relevance, epigenetic regulation, and molecular networks. Methods: Expression data from TCGA, UALCAN, and GSCA were analyzed to compare CCL18 and EGF levels in BRCA and normal tissues. Immune infiltration was assessed using TIMER, while survival analyses were performed via Kaplan-Meier plotter and TCGA subcohorts, including menopausal status. Promoter DNA methylation was examined using UALCAN. Gene correlation networks and protein-protein interactions were assessed using UALCAN and STRING. Result: CCL18 was significantly upregulated in BRCA tissues, while EGF showed no consistent increase compared to normal tissue. Both genes were strongly correlated with immune cell infiltration. High CCL18 and EGF expression was associated with reduced relapse-free survival in BRCA. Promoter regions of both genes exhibited reduced DNA methylation, supporting their elevated expression in tumors. Interaction analyses revealed distinct immune- and signaling-related gene and protein networks. Conclusion: CCL18 shows strong prognostic and immunological relevance in BRCA, while EGF appears to play a broader oncogenic role. Hypomethylation of both genes may drive their aberrant expression and involvement in tumor progression.