Abstract
Changes in glycosphingolipid structures have been shown to occur during the development of several types of human cancers, generating cancer-specific carbohydrate structures that could be used as biomarkers for diagnosis and therapeutic targeting. In this study, we characterized nonacid glycosphingolipids isolated from a human gastric adenocarcinoma by mass spectrometry, enzymatic hydrolysis, and by binding with a battery of carbohydrate-recognizing ligands. We show that the majority of the complex nonacid glycosphingolipids had type 2 (Galβ4GlcNAc) core chains (neolactotetraosylceramide, the Lex, H type 2, x2, and the P1 pentaosylceramides, and the Ley, A type 2, and neolacto hexaosylceramides). We also found glycosphingolipids with type 1 (Galβ3GlcNAc) core (lactotetraosylceramide and the H type 1 pentaosylceramide) and globo (GalαGal) core chains (globotriaosylceramide and globotetraosylceramide). Interestingly, we characterized two complex glycosphingolipids as a P1 heptaosylceramide (Galα4Galβ4GlcNAcβ3Galβ4GlcNAcβ3Gal β4Glcβ1Cer) and a branched P1 decaosylceramide (Galα4Gal β4GlcNAcβ3(Galα4Galβ4GlcNAcβ6)Galβ4GlcNAcβ3Galβ4Glc β1Cer). These are novel glycosphingolipid structures and the first reported cases of complex glycosphingolipids larger than pentaosylceramide carrying the P1 trisaccharide. We propose that these P1 glycosphingolipids may represent potential biomarkers for the early diagnosis of gastric cancer.
Highlights
Gastric adenocarcinoma remains a common cause of cancer death worldwide
H. pylori infection leads to inflammatory changes in the gastric epithelium, and initially causes an acute gastritis, which is followed by chronic gastritis
Journal Pre-proof In the present study non-acid glycosphingolipids isolated from one human gastric adenocarcinoma specimen were characterized by mass spectrometry, enzymatic hydrolysis, and by binding of a battery of carbohydrate recognizing ligands, with special attention to compounds recognized by H. pylori
Summary
Gastric adenocarcinoma remains a common cause of cancer death worldwide. In 2020 there were 1.09 million new cases and 769 000 deaths due to stomach cancer [1]. H. pylori colonization of the human stomach is initiated by binding of bacterial adhesins to carbohydrate receptors on the gastric epithelium. Despite the multitude of candidate H. pylori glycan receptors only three carbohydrate binding adhesins have been characterized to date; the blood group antigen binding BabA adhesin, the sialic acid binding SabA adhesin, and the LabA adhesin BabA of specialist strains binds only to glycoconjugates with unsubstituted terminal Fuc 2Gal sequence as the H type 1 and Leb determinants, whereas the generalist BabA tolerates an addition of Gal. Journal Pre-proof or GalNAc to the Gal, as in the blood group A or B type 1 determinants. Journal Pre-proof In the present study non-acid glycosphingolipids isolated from one human gastric adenocarcinoma specimen were characterized by mass spectrometry, enzymatic hydrolysis, and by binding of a battery of carbohydrate recognizing ligands, with special attention to compounds recognized by H. pylori
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