Serum protein N-glycosylation changes in multiple myeloma

Zhang, Zejian; Westhrin, Marita; Bondt, Albert; Wuhrer, Manfred; Standal, Therese; Holst, Stephanie

doi:10.1016/j.bbagen.2019.03.001

Cited by 36 publications

(60 citation statements)

References 56 publications

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“…As is common practice in comparative glycomics [ 28 , 29 , 61 ], the relative abundance of all 62 N -glycan isomers was determined within each sample using label-free quantitation and the resulting glycan profiles were then compared across all samples, as shown in Supplementary Table S2 . In agreement with literature of the human serum N -glycome [ 41 , 42 , 43 , 44 ], the N -glycome data for all individuals were found to span the three common N -glycan classes including, most prominently, the complex-type N -glycans identified with and without sialylation and fucosylation (~94.5%), and several less abundant oligomannosidic- (~4.0%), and hybrid- (~1.5%) type N -glycans, as shown in Figure 2 b.…”

Section: Resultssupporting

confidence: 91%

“…Protein-bound N -glycans are abundantly present in most if not all accessible bodily fluids including in blood and are therefore recognized as attractive yet still clinically under-utilized marker candidates for a variety of pathophysiological conditions including rheumatoid arthritis [ 40 ], chronic liver cirrhosis [ 41 ], acute pancreatitis [ 42 ], urothelial carcinomas [ 43 ], and multiple myeloma [ 44 ]. Developments in mass spectrometry (MS)-based quantitative N -glycomics including the implementation and improvement of porous graphitized carbon liquid chromatography tandem mass spectrometry (PGC-LC-MS/MS)-based methods to quantitatively profile the glycome with glycan isomer resolution [ 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ] have opened new avenues to test the biomarker potential of glycans for such pathophysiological conditions [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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Serum N-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens

Chatterjee

Kawahara

Tjondro

et al. 2021

JCM

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Bacteremia—i.e., the presence of pathogens in the blood stream—is associated with long-term morbidity and is a potential precursor condition to life-threatening sepsis. Timely detection of bacteremia is therefore critical to reduce patient mortality, but existing methods lack precision, speed, and sensitivity to effectively stratify bacteremic patients. Herein, we tested the potential of quantitative serum N-glycomics performed using porous graphitized carbon liquid chromatography tandem mass spectrometry to stratify bacteremic patients infected with Escherichia coli (n = 11), Staphylococcus aureus (n = 11), Pseudomonas aeruginosa (n = 5), and Streptococcus viridans (n = 5) from healthy donors (n = 39). In total, 62 N-glycan isomers spanning 41 glycan compositions primarily comprising complex-type core fucosylated, bisecting N-acetylglucosamine (GlcNAc), and α2,3-/α2,6-sialylated structures were profiled across all samples using label-free quantitation. Excitingly, unsupervised hierarchical clustering and principal component analysis of the serum N-glycome data accurately separated the patient groups. P. aeruginosa-infected patients displayed prominent N-glycome aberrations involving elevated levels of fucosylation and bisecting GlcNAcylation and reduced sialylation relative to other bacteremic patients. Notably, receiver operating characteristic analyses demonstrated that a single N-glycan isomer could effectively stratify each of the four bacteremic patient groups from the healthy donors (area under the curve 0.93–1.00). Thus, the serum N-glycome represents a new hitherto unexplored class of potential diagnostic markers for bloodstream infections.

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Section: Resultssupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Serum N-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens

Chatterjee

Kawahara

Tjondro

et al. 2021

JCM

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“…It has been recently shown that the monoclonal immunoglobulins secreted by the malignant plasma cells display an aberrant glycosylation pattern (Zhang Z. et al, 2019). In particular, a detailed analysis of the total protein N -glycans derived from serum samples of MM patients showed a decrease in the α2-3- and α2-6-linked sialic acids on secreted monoclonal immunoglobulins.…”

Section: Role Of Sialylation In the Biology Of Myelomamentioning

confidence: 99%

Targeted Approaches to Inhibit Sialylation of Multiple Myeloma in the Bone Marrow Microenvironment

Natoni

Bohara

Pandit

et al. 2019

Front. Bioeng. Biotechnol.

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Aberrant glycosylation modulates different aspects of tumor biology, and it has long been recognized as a hallmark of cancer. Among the different forms of glycosylation, sialylation, the addition of sialic acid to underlying oligosaccharides, is often dysregulated in cancer. Increased expression of sialylated glycans has been observed in many types of cancer, including multiple myeloma, and often correlates with aggressive metastatic behavior. Myeloma, a cancer of plasma cells, develops in the bone marrow, and colonizes multiple sites of the skeleton including the skull. In myeloma, the bone marrow represents an essential niche where the malignant cells are nurtured by the microenvironment and protected from chemotherapy. Here, we discuss the role of hypersialylation in the metastatic process focusing on multiple myeloma. In particular, we examine how increased sialylation modulates homing of malignant plasma cells into the bone marrow by regulating the activity of molecules important in bone marrow cellular trafficking including selectins and integrins. We also propose that inhibiting sialylation may represent a new therapeutic strategy to overcome bone marrow-mediated chemotherapy resistance and describe different targeted approaches to specifically deliver sialylation inhibitors to the bone marrow microenvironment.

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“…For the past few years, serological glycomic profiling provides a new approach for the discovery of non-invasive biomarkers. The total plasma protein N-glycome has been increasingly reported to have great potential as biomarkers in a multitude of diseases, especially cancer (15,(21)(22)(23)(24). Several studies have indicated associations between abnormal glycosylation and TC (25)(26)(27), which exemplified a biomarker potential of the altered glycans.…”

Section: Introductionmentioning

confidence: 99%

Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma N-Glycomics

Zhang

Reiding

et al. 2021

Front. Endocrinol.

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BackgroundBiomarkers are needed for patient stratification between benign thyroid nodules (BTN) and thyroid cancer (TC) and identifying metastasis in TC. Though plasma N-glycome profiling has shown potential in the discovery of biomarkers and can provide new insight into the mechanisms involved, little is known about it in TC and BTN. Besides, several studies have indicated associations between abnormal glycosylation and TC. Here, we aimed to explore plasma protein N-glycome of a TC cohort with regard to their applicability to serve as biomarkers.MethodsPlasma protein N-glycomes of TC, BTN, and matched healthy controls (HC) were obtained using a robust quantitative strategy based on MALDI-TOF MS and included linkage-specific sialylation information.ResultsPlasma N-glycans were found to differ between BTN, TC, and HC in main glycosylation features, namely complexity, galactosylation, fucosylation, and sialylation. Four altered glycan traits, which were consecutively decreased in BTN and TC, and classification models based on them showed high potential as biomarkers for discrimination between BTN and TC (“moderately accurate” to “accurate”). Additionally, strong associations were found between plasma N-glycans and lymph node metastasis in TC, which added the accuracy of predicting metastasis before surgery to the existing method.ConclusionsWe comprehensively evaluated the plasma N-glycomic changes in patients with TC or BTN for the first time. We determined several N-glycan biomarkers, some of them have potential in the differential diagnosis of TC, and the others can help to stratify TC patients to low or high risk of lymph node metastasis. The findings enhanced the understanding of TC.

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Serum protein N-glycosylation changes in multiple myeloma

Cited by 36 publications

References 56 publications

Serum N-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens

Serum N-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens

Targeted Approaches to Inhibit Sialylation of Multiple Myeloma in the Bone Marrow Microenvironment

Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma N-Glycomics

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