Occurrence of a d-arabinose-containing complex-type free-N-glycan in the urine of cancer patients

Abstract

Urinary free-glycans are promising markers of disease. In this study, we attempted to identify novel tumor markers by focusing on neutral free-glycans in urine. Free-glycans extracted from the urine of normal subjects and cancer patients with gastric, colorectal, pancreatic and bile duct were fluorescently labeled with 2-aminopyridine. Profiles of these neutral free-glycans constructed using multidimensional high performance liquid chromatography separation were compared between normal controls and cancer patients. The analysis identified one glycan in the urine of cancer patients with a unique structure, which included a pentose residue. To reveal the glycan structure, the linkage fashion, monosaccharide species and enantiomer of the pentose were analyzed by high performance liquid chromatography and mass spectrometry combined with several chemical treatments. The backbone of the glycan was a monoantennary complex-type free-N-glycan containing β1,4-branch. The pentose residue was attached to the antennal GlcNAc and released by α1,3/4-l-fucosidase. Intriguingly, the pentose residue was consistent with d-arabinose. Collectively, this glycan structure was determined to be Galβ1-4(d-Araβ1-3)GlcNAcβ1-4Manα1-3Manβ1-4GlcNAc-PA. Elevation of d-arabinose-containing free-glycans in the urine of cancer patients was confirmed by selected reaction monitoring. This is the first study to unequivocally show the occurrence of a d-arabinose-containing oligosaccharide in human together with its detailed structure.

Rat hepatocytes secrete free oligosaccharides

“…In sharp contrast, virtually nothing is known regarding the mechanism for how extracellular free glycans are formed. While previous studies indicated that extracellular FNGs in sera or urine may represent novel disease biomarkers ( 5 , 6 , 7 , 8 , 10 ), our current study suggests that the secretion of various types of serum-free glycans, that is, not only FNGs but also free lactose/LacNAc-type glycans, can be theoretically correlated with the conditions of the liver, from which those glycans are secreted.…”

“…In recent years, sialyl free oligosaccharides have been identified in the serum as well as in urine samples in human and various animals ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ). Changes in some specific structures of sialyl free N -glycans (FNGs) have been shown to be related to the growth status of animals, and the overall levels of serum sialyl FNGs has also been shown to be increased in patients with certain types of liver disease ( 10 ), implying a close relationship between glycan catabolism and the pathophysiological conditions of the liver.…”

Pectinose induces cell cycle arrest in luminal A and triple-negative breast cancer cells by promoting autophagy through activation of the p38 MAPK signaling pathway

“…D-arabinose is unlike other monosaccharides, as humans cannot derive it naturally from food. Although D-arabinose contributes to the regulation of various biological activities, such as metabolism and cell proliferation, there was previously no direct evidence suggesting that D-arabinose has anti-cancer effects by inhibiting tumor cell growth [22,23]. In present study, we found that D-arabinose could significantly restrict the proliferation of breast cancer cells in vivo and in vitro.…”