Abstract
To enhance breast cancer (BC) management, there is an urgent need for molecular prognostic markers and therapeutic targets. This study investigates the role of chondroadherin (CHAD) in BC prognosis and its potential as a therapeutic target, focusing on its correlation with cancer severity and patient survival. CHAD expression at both mRNA and protein levels was analyzed in multiple datasets, and survival analysis was conducted. Comparisons were made between groups with different metastasis tendencies, and associations with clinical and pathological stages were examined. CHAD knockdown in T47D and ZR75-30 cell lines was performed to assess effects on proliferation and migration. Overexpression of CHAD in the MDA-MB-231 cell line reduced cell proliferation capability. GO/KEGG enrichment analysis identified CHAD's roles in molecular functions, cellular components, and biological processes. Western blotting evaluated CHAD's impact on the PI3K/Akt signaling pathway. Results indicated that CHAD expression is significantly lower in high malignancy BC groups and is associated with poorer survival outcomes. Increased CHAD levels correlate with lower metastasis propensity and are typically seen in lower-grade BC patients. CHAD knockdown increased proliferation and migration in T47D and ZR75-30 cells. Enrichment analyses highlighted pathways like "focal adhesion," "ECM receptor interaction," "regulation of actin cytoskeleton," and "PI3K/Akt pathway." Western blotting confirmed that CHAD inhibits PI3K and Akt phosphorylation. In summary, CHAD serves as a tumor suppressor gene and potential prognostic biomarker in breast cancer by inhibiting cell migration and proliferation through cell adhesion and PI3K/Akt pathway inhibition. Reduced CHAD expression correlates with worse prognosis, suggesting its potential as a therapeutic target.