Identification of a free-N-glycan with difucosylated type-1 lactosamine in cancerous tissue and its validation for cancer diagnosis by urinary testing

Numerous urinary acidic free-glycan tumor marker candidates have been identified based on the glycan structure profiles of human cancer tissues. In this study, to identify novel glycan tumor markers, we performed precise glycan structural analysis focusing on neutral free-glycans in colorectal cancer tissues. Our analysis detected one free-glycan that was significantly elevated in colorectal cancer cells by comparison to the corresponding normal epithelial cells. Structural studies of this glycan revealed it to comprise a free-N-glycan with a difucosylated type-1 lactosamine structure (Lewis B antigen), rather than a conventional type-2 lactosamine structure. The presence of N-glycans with type-1 lactosamine structure has rarely been reported in humans. To investigate its clinical usefulness, the level of this free-glycan in the urine of 121 healthy subjects, 141 gastric cancer patients, 87 colorectal cancer patients, 55 pancreatic cancer patients, 13 bile duct cancer patients and 79 rare cancer patients were measured using a liquid chromatography-selected reaction monitoring assay. Significant differences were detected in cancer patient samples compared to healthy controls, with a marked increase in some rare-types of cancer patient samples, such as AFP-producing gastric cancer.