Metabolic-Immuno-Hormonal Cross-talk in Breast Cancer: A UAE-Based Multi-Omics Perspective.

Breast cancer (BC) remains the leading cause of cancer-related death among women in the Middle East and North Africa, with particularly high mortality in the United Arab Emirates (UAE), mainly due to delayed diagnosis. This study aimed to identify metabolic and proteomic biomarkers associated with BC progression in the UAE population. A cohort of 35 BC patients and 30 healthy control (HC) individuals underwent plasma-based untargeted metabolomics and proteomics analyses using LC-QTOF-MS. Multivariate statistical models, including OPLS-DA and AUROC analyses, were employed to assess biomarker performance. Integrated pathway and structural motif analyses were conducted to explore disease-stage-specific signatures. A distinct metabolic signature was identified, featuring disrupted amino acid (particularly arginine), purine/pyrimidine, and steroid hormone metabolism. Key metabolites such as l-arginine, hypoxanthine, uridine, vitamin D3, and estradiol showed stage-specific alterations. Eleven metabolites yielded high diagnostic power (AUROC = 0.954). Structural motif analysis revealed a transition from small, polar metabolites in early-stage BC to complex, lipophilic steroidal, and lipid structures in late-stage disease. Integrated proteomics revealed dysregulated immune and hormonal signaling, highlighting the cross-talk among metabolic, immune, and endocrine pathways. This UAE-based study reveals distinct metabolic and structural features of BC progression, suggesting candidate biomarkers for BC detection and personalized therapy.