Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas

Tanaka, Toshikazu; Yoneyama, T.; Noro, Daisuke; Imanishi, Kengo; Kojima, Yuta; Hatakeyama, Shingo; Tobisawa, Yuki; Mori, Kazuyuki; Yamamoto, Hayato; Imai, Atsushi; Yoneyama, Takahiro; Hashimoto, Yasuhiro; Koie, Takuya; Tanaka, Masakazu; Nishimura, Shin‐Ichiro; Kurauchi, Shizuka; Takahashi, Ippei; Οhyama, Chikara

doi:10.3390/ijms18122632

Cited by 29 publications

(18 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The relative quantification of the N-glycan species that constitute the sugar shell of circulating proteins is a wealthy source of reliable biomarkers. The characterization of circulating N-glycans from sera or plasma, hereafter referred as glycomics, has provided markers in several clinical fields such as hepatology ( 247 – 249 ), type 2 diabetes ( 250 – 254 ), RA ( 255 – 258 ), and cancer ( 259 – 262 ).…”

Section: Markers Of Biological Agementioning

confidence: 99%

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

et al. 2018

View full text Add to dashboard Cite

Geroscience, the new interdisciplinary field that aims to understand the relationship between aging and chronic age-related diseases (ARDs) and geriatric syndromes (GSs), is based on epidemiological evidence and experimental data that aging is the major risk factor for such pathologies and assumes that aging and ARDs/GSs share a common set of basic biological mechanisms. A consequence is that the primary target of medicine is to combat aging instead of any single ARD/GSs one by one, as favored by the fragmentation into hundreds of specialties and sub-specialties. If the same molecular and cellular mechanisms underpin both aging and ARDs/GSs, a major question emerges: which is the difference, if any, between aging and ARDs/GSs? The hypothesis that ARDs and GSs such as frailty can be conceptualized as accelerated aging will be discussed by analyzing in particular frailty, sarcopenia, chronic obstructive pulmonary disease, cancer, neurodegenerative diseases such as Alzheimer and Parkinson as well as Down syndrome as an example of progeroid syndrome. According to this integrated view, aging and ARDs/GSs become part of a continuum where precise boundaries do not exist and the two extremes are represented by centenarians, who largely avoided or postponed most ARDs/GSs and are characterized by decelerated aging, and patients who suffered one or more severe ARDs in their 60s, 70s, and 80s and show signs of accelerated aging, respectively. In between these two extremes, there is a continuum of intermediate trajectories representing a sort of gray area. Thus, clinically different, classical ARDs/GSs are, indeed, the result of peculiar combinations of alterations regarding the same, limited set of basic mechanisms shared with the aging process. Whether an individual will follow a trajectory of accelerated or decelerated aging will depend on his/her genetic background interacting lifelong with environmental and lifestyle factors. If ARDs and GSs are manifestations of accelerated aging, it is urgent to identify markers capable of distinguishing between biological and chronological age to identify subjects at higher risk of developing ARDs and GSs. To this aim, we propose the use of DNA methylation, N-glycans profiling, and gut microbiota composition to complement the available disease-specific markers.

show abstract

Section: Markers Of Biological Agementioning

confidence: 99%

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

et al. 2018

View full text Add to dashboard Cite

show abstract

“…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%

Serum N-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens

Chatterjee

Kawahara

Tjondro

et al. 2021

JCM

View full text Add to dashboard Cite

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.

show abstract

“…Altered glycosylation has been aligned with carcinogenesis, progression of the disease, tumor associated invasion, sensitivity to treatment [ 6 – 9 ]. Cancer specific changes in glycosylation can serve as diagnostic as well as therapeutic targets, for instance aberrant N-glycosylation of serum Immunoglobulins (Igs) urothelial carcinoma suggests glycosylation pattern as diagnostic biomarker [ 10 , 11 ]. Dysregulation of protein glycosylation has been associated with cancer hallmarks in bladder cancer [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Urinary glycoproteomic profiling of non-muscle invasive and muscle invasive bladder carcinoma patients reveals distinct N-glycosylation pattern of CD44, MGAM, and GINM1

et al. 2020

View full text Add to dashboard Cite

Clinical management of bladder carcinomas (BC) remains a major challenge and demands comprehensive multi-omics analysis for better stratification of the disease. Identification of patients on risk requires identification of signatures predicting prognosis risk of the patients. Understanding the molecular alterations associated with the disease onset and progression could improve the routinely used diagnostic and therapy procedures. In this study, we investigated the aberrant changes in N-glycosylation pattern of proteins associated with tumorigenesis as well as disease progression in bladder cancer. We integrated and compared global N-glycoproteomic and proteomic profile of urine samples from bladder cancer patients at different clinicopathological stages (non-muscle invasive and muscleinvasive patients [n = 5 and 4 in each cohort]) with healthy subjects (n = 5) using SPEG method. We identified 635 N-glycopeptides corresponding to 381 proteins and 543 N-glycopeptides corresponding to 326 proteins in NMIBC and MIBC patients respectively. Moreover, we identified altered glycosylation in 41 NMIBC and 21 MIBC proteins without any significant change in protein abundance levels. In concordance with the previously published bladder cancer cell line N-glycoproteomic data, we also observed dysregulated glycosylation in ECM related proteins. Further, we identified distinct N-glycosylation pattern of CD44, MGAM, and GINM1 between NMIBC and MIBC patients, which may be associated with disease progression in bladder cancer. These aberrant protein glycosylation events would provide a novel approach for bladder carcinoma diagnosis and further define novel mechanisms of tumor initiation and progression.

show abstract

Aberrant N-Glycosylation Profile of Serum Immunoglobulins is a Diagnostic Biomarker of Urothelial Carcinomas

Cited by 29 publications

References 33 publications

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates

Serum N-Glycomics Stratifies Bacteremic Patients Infected with Different Pathogens

Urinary glycoproteomic profiling of non-muscle invasive and muscle invasive bladder carcinoma patients reveals distinct N-glycosylation pattern of CD44, MGAM, and GINM1

Contact Info

Product

Resources

About