Comprehensive Glycomic Profiling of Breast Cancer Patients.

Glycans are complex carbohydrates found on extracellular membrane lipids and proteins. They are known to be variably expressed by cancer cells, which can have partial or even novel glycan structures. Therefore, we hypothesize that the analysis of breast cancer patient glycomic profiles will result in elucidation of specific and generalizable signatures which will be useful for the diagnosis and treatment of breast cancer. Our study examines N-glycan expression and its changes through breast cancer stages and compares them to healthy donor samples to create a catalogue of changes and profiles based on cancer stage and other tumor attributes. We are specifically investigating N-glycans found in patient serum, on the tumor cells, and on adjacent normal tissue. Serum and tissue (tumor and normal) samples from breast cancer patients were analyzed using mass spectroscopy to determine the presence, type, and amount of over 300 unique glycan compositions. Bioinformatic analysis is being used to develop comprehensive glycomic profiles of patients and glycan signatures of cancer stages. We have found several sets of glycan compositions in the serum that appear to change over the progression of cancer. Most notably, glycans of low molecular mass (H4N2, H3N3, H5N2, H3N3F1, H4N3, H3N4, H3N5, H5N5) are rarely present in healthy samples, but are prevalent in all 4 stages of cancer patients. Alternatively, several glycans of varying molecular weight have low expression in healthy patients but higher expression in cancer patients (H4N4F1, H6N2, H5N4F1, H3N4F1, H5N4, H5N2, H4N5F1). Comparing serum and tumor glycan profiles to those of healthy sera and tissue controls will allow for a more comprehensive understanding of the aberrant expression of glycan structures in breast cancer. The collected information has the potential for more accurate diagnoses and personalized treatments. Prospective uses of differential glycomic profiles could allow oncologists and their patients a more nuanced understanding of the tumor and its characteristics.