Decreased Core-Fucosylation Contributes to Malignancy in Gastric Cancer

Zhao, Yunpeng; Xu, Xinyun; Fang, Meng; Wang, Hao; You, Qi; Yi, Chenju; Ji, Jun Ho; Gu, Xing; Zhou, Pingting; Cheng, Cheng; Gao, Chunfang

doi:10.1371/journal.pone.0094536

Cited by 82 publications

(67 citation statements)

References 36 publications

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“…DSA-FACE is a simple and efficient technology for measuring N-glycan changes in serum. We previously used the technology to assist in the diagnosis of HCC, CRC, and gastric cancer [29][30][31]. The study was designed to target analysis of the aberrant N-glycans.…”

Section: Discussionmentioning

confidence: 99%

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

Zhao

Zhou

et al. 2015

Clin Exp Med

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Pancreatic cancer (PC) has a high mortality rate because it is usually diagnosed late. Glycosylation of proteins is known to change in tumor cells during the development of PC. The objectives of this study were to identify and validate the diagnostic value of novel biomarkers based on N-glycomic profiling for PC. In total, 217 individuals including subjects with PC, pancreatitis, and healthy controls were divided randomly into a training group (n = 164) and validation groups (n = 53). Serum N-glycomic profiling was analyzed by DSA-FACE. The diagnostic model was constructed based on N-glycan markers with logistic stepwise regression. The diagnostic performance of the model was assessed further in validation cohort. The level of total core fucose residues was increased significantly in PC. Two diagnostic models designated GlycoPCtest and PCmodel (combining GlycoPCtest and CA19-9) were constructed to differentiate PC from normal. The area under the receiver operating characteristic curve (AUC) of PCmodel was higher than that of CA19-9 (0.925 vs. 0.878). The diagnostic models based on N-glycans are new, valuable, noninvasive alternatives for identifying PC. The diagnostic efficacy is improved by combined GlycoPCtest and CA19-9 for the discrimination of patients with PC from healthy controls.

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Section: Discussionmentioning

confidence: 99%

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

Zhao

Zhou

et al. 2015

Clin Exp Med

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“…FUCA1 is an enzyme which cleaves terminal fucose in glycan chains. It is involved in several cancers like breast cancer (22), colorectal cancer (23) and gastric cancer, exhibiting down-regulation (25). The up-regulation of FUCA1 in SiHa vs. HCK1T was also confirmed with western blot analysis.…”

Section: Discussionmentioning

confidence: 64%

“…FUCA1 was particularly chosen for validation as it plays an active role in human carcinogenesis (22)(23)(24)(25). Specifically proteomics analysis showed significant up-regulation in SiHa (49.4-fold change, p<0.05), when compared to HCK1T.…”

Section: Resultsmentioning

confidence: 99%

High Resolution Proteomic Analysis of the Cervical Cancer Cell Lines Secretome Documents Deregulation of Multiple Proteases

Pappa

Kontostathi

Makridakis

et al. 2017

CGP

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Abstract. Background: Oncogenic infection by HPVThe vast majority of cervical cancer incidents are related to a group of 13 high-risk oncogenic human papilloma virus (HPV) types, classified according to sequence similarity, based on established criteria by the International Committee on the Taxonomy of Viruses (1). Types HPV16 and HPV18 represent the most common high-risk types causing cervical cancer (2, 3). Microabrasions on the cervical epithelium surface, allow the entry of HPV and the ensuing infection of the basal membrane epithelium. The initial overexpression of E6 and E7 HPV oncoproteins in the upper layers of the epithelium, leads to the production of viral particles and the establishment of productive infection, associated with the formation of low-grade squamous intraepithelial lesions (LSIL). Subsequent integration of the virus in the host cells, results in progression to high-grade squamous intraepithelial lesions (HSIL), leading eventually to cervical cancer (4-7).Proteomics technologies offer an holistic approach through the identification of many critical proteins, that could facilitate the understanding of biological mechanisms underlying cervical cancer pathogenesis. Proteomic tools have been utilized to study the mechanisms of action of drugs and the discovery of putative biomarkers for cervical cancer (8). However, in the above approaches, only the two-dimensional gel electrophoresis (2DE) coupled to MALDI-TOF has been utilized in most studies so far, whereas the LC-MS/MS technology, a very sensitive technology, has not been widely used. Furthermore, in these few studies where LC-MS/MS was applied, only the intracellular proteome was analyzed, 507

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“…4. The charge-to-size ratio can also be altered through a change in the charge of the molecules, as is the case for glucose-6-phosphate dehydrogenase conversion of NAD+ to NADH [22,23], aminotransferase transfer of an amine group from L-valine to α-ketogluterate [24], xanthine oxidase oxidation of 6-mercaptopurine to 6-thioric acid [25], and neuraminidase removal of sialic acids from glycans [26], including those found in tumor tissues and serum samples [27]. While the change in charge changes the charge-to-size ratio of NADH and NAD+ to enable separation, researchers can still utilize the difference in the spectroscopic properties of these molecules to quantify only NADH at 340 nm [22,23].…”

Section: Adapting the Separation To Determine Km Valuesmentioning

confidence: 99%

“…This is observed as a shift in the substrate peak as compared to the separation performed in the absence of the enzyme. The use of multiple exoglycosidase has enabled the determination of terminal glycan identities [27,97]. Szigeti and Guttman successfully performed analyses using automated sample preparation prior to the capillary electrophoresis analysis [97].…”

Section: Emerging Techniques and Future Directionsmentioning

confidence: 99%

Advances in enzyme substrate analysis with capillary electrophoresis

Gattu

Crihfield

et al. 2018

Methods

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Capillary electrophoresis provides a rapid, cost-effective platform for enzyme and substrate characterization. The high resolution achievable by capillary electrophoresis enables the analysis of substrates and products that are indistinguishable by spectroscopic techniques alone, while the small volume requirement enables analysis of enzymes or substrates in limited supply. Furthermore, the compatibility of capillary electrophoresis with various detectors makes it suitable for KM determinations ranging from nanomolar to millimolar concentrations. Capillary electrophoresis fundamentals are discussed with an emphasis on the separation mechanisms relevant to evaluate sets of substrate and product that are charged, neutral, and even chiral. The basic principles of Michaelis-Menten determinations are reviewed and the process of translating capillary electrophoresis electropherograms into a Michaelis-Menten curve is outlined. The conditions that must be optimized in order to couple off-line and on-line enzyme reactions with capillary electrophoresis separations, such as incubation time, buffer pH and ionic strength, and temperature, are examined to provide insight into how the techniques can be best utilized. The application of capillary electrophoresis to quantify enzyme inhibition, in the form of KI or IC50 is detailed. The concept and implementation of the immobilized enzyme reactor is described as a means to increase enzyme stability and reusability, as well as a powerful tool for screening enzyme substrates and inhibitors. Emerging techniques focused on applying capillary electrophoresis as a rapid assay to obtain structural identification or sequence information about a substrate and in-line digestions of peptides and proteins coupled to mass spectrometry analyses are highlighted.

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Decreased Core-Fucosylation Contributes to Malignancy in Gastric Cancer

Cited by 82 publications

References 36 publications

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

Validation of N-glycan markers that improve the performance of CA19-9 in pancreatic cancer

High Resolution Proteomic Analysis of the Cervical Cancer Cell Lines Secretome Documents Deregulation of Multiple Proteases

Advances in enzyme substrate analysis with capillary electrophoresis

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