Ketodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to... Show moreKetodeoxynononic acid (Kdn) is a rather uncommon class of sialic acid in mammals. However, associations have been found between elevated concentrations of free or conjugated Kdn in relation to human cancer progression. Hitherto, there has been a lack of conclusive evidence that Kdn occurs on (specific) human glycoproteins (conjugated Kdn). Here, we report for the first time that Kdn is expressed on prostate-specific antigen (PSA) N-linked glycans derived from human seminal plasma and urine. Interestingly, Kdn was found only in an α2,3-linkage configuration on an antennary galactose, indicating a highly specific biosynthesis. This unusual glycosylation feature was also identified in a urinary PSA cohort in relation to prostate cancer (PCa), although no differences were found between PCa and non-PCa patients. Further research is needed to investigate the occurrence, biosynthesis, biological role, and biomarker potential of both free and conjugated Kdn in humans. Show less
Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the... Show moreAberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans. Show less
He, M.; Sun, M.M.; Koval, S.; Wijk, R. van; Hankemeier, T.; Greef, J. van der; ... ; Wang, M. 2019
The prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Because of the limited success of generic interventions, the focus of the disease study has shifted toward... Show moreThe prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly worldwide. Because of the limited success of generic interventions, the focus of the disease study has shifted toward personalized strategies, particularly in the early stages of the disease. Traditional Chinese medicine (TCM) is based on a systems view combined with personalized strategies and has improved our knowledge of personalized diagnostics. From a systems biology perspective, the understanding of personalized diagnostics can be improved to yield a biochemical basis for such strategies; for example, metabolomics can be used in combination with other system-based diagnostic methods such as ultra-weak photon emission (UPE). In this study, we investigated the feasibility of using plasma metabolomics obtained from 44 pre-T2DM subjects to stratify the following TCM-based subtypes: Qi-Yin deficiency, Qi-Yin deficiency with dampness, and Qi-Yin deficiency with stagnation. We studied the relationship between plasma metabolomics and UPE with respect to TCM-based subtyping in order to obtain biochemical information for further interpreting disease subtypes. Principal component analysis of plasma metabolites revealed differences among the TCM-based pre-T2DM subtypes. Relatively high levels of lipids (e.g., cholesterol esters and triglycerides) were important discriminators of two of the three subtypes and may be associated with a higher risk of cardiovascular disease. Plasma metabolomics data indicate that the lipid profile is an essential component captured by UPE with respect to stratifying subtypes of T2DM. The results suggest that metabolic differences exist among different TCM-based subtypes of pre-T2DM, and profiling plasma metabolites can be used to discriminate among these subtypes. Plasma metabolomics thus provides biochemical insights into system-based UPE measurements. (C) 2019 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company. Show less
