Complex Carbohydrates As A Predictive Marker In Metastatic Colorectal Cancer (Mcrc) Cancer Patients Treated With A Vascular Endothelial Growth Factor (Vegf) Inhibitor And Chemotherapy.

e15134 Background: Aberrant expression of complex carbohydrates, known as glycans, is emerging as a key driver in oncopathology. Elevated levels of sialic acid sugars affect tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. Changes in sialylation can be associated with malignant transformation and with progression and poor prognosis of carcinomas, which can be explained by the recognition of malignant cells by selectins, causing interactions of tumor cells with platelets, leukocytes and endothelium facilitating metastasis. Secreted or proteolytically released carcinoma mucins bearing unusual forms of sialylation can be detected in the bloodstream and are used as diagnostic and prognostic aids. Bevacizumab directly binds VEGF (a glycoprotein) to inhibit angiogenesis. The aim of this study was to analyze the pool of asparagine-linked complex carbohydrates (i.e. the N-glycome), of whole serum to identify sugars that are associated with survival in mCRC patients treated with a VEGF and chemotherapy. Methods: We used our recently developed high-throughput automated platform to precisely measure the levels of complex serum carbohydrates in patients (n = 68) with metastatic colorectal cancer samples of patients who went on to receive bevacizumab and chemotherapy. Survival analysis was performed using the R package ‘survival’. Results: We observed several sialic-acid bearing glycans that correlated with overall survival and progression free survival. A complex tetra-antennary, highly sialylated glycan, known as A4G4S4, correlated with reduced overall survival probability (p = 0.0007, hazard ratio = 1.86). High levels of a sialylated tri-antennary glycan, called A3G3S3 demonstrated significantly reduced progression-free survival (p = 0.002). Conclusions: We believe that sialylated glycans could be excellent predictive markers of response to therapy and warrant further evaluation in clinical trials. Tri and tetra-antennary sialyated glycoproteins were associated with poorer survival in our patient cohort, suggesting that glycans could be key drivers of pathobiology.