Glycan Analysis of Serum and Breast Tissue Identifies Potential Biomarkers of Cancer Subtype and Severity

Breast cancer is the most prevalent cancer among women and one of the leading causes of cancer mortality. Early detection and accurate staging are essential for improving survival rates, yet current methods heavily rely on invasive biopsies. Glycoproteins, crucial biomarkers in various cancers, offer a minimally invasive diagnostic alternative. This pilot study employed MALDI-TOF mass spectrometry to analyze the glycomic profiles of breast tissue and serum samples from 39 breast cancer patients and 10 healthy controls. Over 300 unique glycans were identified, with significant elevations of high mannose glycans observed in malignant tissue and serum compared to healthy controls (p< 0.0001). Moreover, high-mannose glycan levels correlated with advanced cancer stages (p< 0.001) and poor differentiation grades (p< 0.05). HER2-positive and ER-negative tumors dis-played distinct glycosylation patterns, indicating potential molecular subtypes. Notably, serum levels of specific complex N-glycans, H3N5F1 and H4N5F1, declined significantly with disease progression, underscoring their potential as biomarkers. These findings suggest that glycomic profiling could revolutionize breast cancer diagnostics, enabling earlier detection, disease monitoring, and molecular subtyping. Further investigation is warranted to validate these biomarkers and elucidate their mechanistic roles in breast cancer pathogenesis.