Glycan analysis of serum and breast tissue identifies potential biomarkers of cancer subtype and severity

BACKGROUND: 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. METHODS: This pilot study employed MALDI-TOF mass spectrometry to analyze and compare the glycomic profiles of tissue and serum samples from breast cancer patients and healthy controls. RESULTS: Over 300 unique glycans were screened, and 61 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 displayed distinct glycosylation patterns, indicating potential molecular subtypes. Notably, serum levels of specific complex N-glycans, H3N5F1, H3N5, H4N5F1,and H4N4, declined significantly with disease progression, underscoring their potential as biomarkers. CONCLUSION: These findings suggest that glycomic profiling could transform breast cancer diagnostics, enabling earlier detection, molecular subtyping, and disease monitoring. Further investigation is warranted to validate these biomarkers and elucidate their mechanistic roles in breast cancer pathogenesis.