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Liu S, Huang J, Liu Y, Lin J, Zhang H, Cheng L, Ye W, Liu X. Identification of serum N-glycans signatures in three major gastrointestinal cancers by high-throughput N-glycome profiling. Clin Proteomics 2024; 21:64. [PMID: 39609732 PMCID: PMC11604001 DOI: 10.1186/s12014-024-09516-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Accepted: 11/19/2024] [Indexed: 11/30/2024] Open
Abstract
BACKGROUND Alternative N-glycosylation of serum proteins has been observed in colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC), while comparative study among those three cancers has not been reported before. We aimed to identify serum N-glycans signatures and introduce a discriminative model across the gastrointestinal cancers. METHODS The study population was initially screened according to the exclusion criteria process. Serum N-glycans profiling was characterized by a high-throughput assay based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Diagnostic model was built by random forest, and unsupervised machine learning was performed to illustrate the differentiation between the three major gastrointestinal (GI) cancers. RESULTS We have found that three major gastrointestinal cancers strongly associated with significantly decreased mannosylation and mono-galactosylation, as well as increased sialylation of serum glycoproteins. A highly accurate discriminative power (> 0.90) for those gastrointestinal cancers was obtained with serum N-glycome based predictive model. Additionally, serum N-glycome profile exhibited distinct distributions across GI cancers, and several altered N-glycans were hyper-regulated in each specific disease. CONCLUSIONS Serum N-glycome profile was differentially expressed in three major gastrointestinal cancers, providing a new clinical tool for cancer diagnosis and throwing a light upon the disease-specific molecular signatures.
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Affiliation(s)
- Si Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122, China
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, No. 1037 Luoyudong Road, Hongshan District, Wuhan, 430074, China
| | - Jianmin Huang
- Digestive Endoscopy Center, South Branch of Fujian Provincial Hospital, Fuzhou, 350000, China
| | - Yuanyuan Liu
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, No. 1037 Luoyudong Road, Hongshan District, Wuhan, 430074, China
| | - Jiajing Lin
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, No. 1037 Luoyudong Road, Hongshan District, Wuhan, 430074, China
| | - Haobo Zhang
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, No. 1037 Luoyudong Road, Hongshan District, Wuhan, 430074, China
| | - Liming Cheng
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430074, China
| | - Weimin Ye
- Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, 350122, China.
| | - Xin Liu
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, No. 1037 Luoyudong Road, Hongshan District, Wuhan, 430074, China.
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Si YT, Xiong XS, Wang JT, Yuan Q, Li YT, Tang JW, Li YN, Zhang XY, Li ZK, Lai JX, Umar Z, Yang WX, Li F, Wang L, Gu B. Identification of chronic non-atrophic gastritis and intestinal metaplasia stages in the Correa's cascade through machine learning analyses of SERS spectral signature of non-invasively-collected human gastric fluid samples. Biosens Bioelectron 2024; 262:116530. [PMID: 38943854 DOI: 10.1016/j.bios.2024.116530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 06/13/2024] [Accepted: 06/15/2024] [Indexed: 07/01/2024]
Abstract
The progression of gastric cancer involves a complex multi-stage process, with gastroscopy and biopsy being the standard procedures for diagnosing gastric diseases. This study introduces an innovative non-invasive approach to differentiate gastric disease stage using gastric fluid samples through machine-learning-assisted surface-enhanced Raman spectroscopy (SERS). This method effectively identifies different stages of gastric lesions. The XGBoost algorithm demonstrates the highest accuracy of 96.88% and 91.67%, respectively, in distinguishing chronic non-atrophic gastritis from intestinal metaplasia and different subtypes of gastritis (mild, moderate, and severe). Through blinded testing validation, the model can achieve more than 80% accuracy. These findings offer new possibilities for rapid, cost-effective, and minimally invasive diagnosis of gastric diseases.
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Affiliation(s)
- Yu-Ting Si
- Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu Province, China
| | - Xue-Song Xiong
- Huai'an Hospital Affiliated to Yangzhou University (The Fifth People's Hospital of Huai'an), Huai'an, Jiangsu Province, China
| | - Jin-Ting Wang
- Huai'an Hospital Affiliated to Yangzhou University (The Fifth People's Hospital of Huai'an), Huai'an, Jiangsu Province, China
| | - Quan Yuan
- School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Yu-Ting Li
- Huai'an Hospital Affiliated to Yangzhou University (The Fifth People's Hospital of Huai'an), Huai'an, Jiangsu Province, China
| | - Jia-Wei Tang
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China; Division of Microbiology and Immunology, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia
| | - Yong-Nian Li
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Xin-Yu Zhang
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Zheng-Kang Li
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Jin-Xin Lai
- Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
| | - Zeeshan Umar
- Marshall Laboratory of Biomedical Engineering, School of Medicine, Shenzhen University, Guangdong Province, China
| | - Wei-Xuan Yang
- Huai'an Hospital Affiliated to Yangzhou University (The Fifth People's Hospital of Huai'an), Huai'an, Jiangsu Province, China
| | - Fen Li
- Huai'an Hospital Affiliated to Yangzhou University (The Fifth People's Hospital of Huai'an), Huai'an, Jiangsu Province, China.
| | - Liang Wang
- School of Medical Informatics and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China; Division of Microbiology and Immunology, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia; The Center for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western Australia, 6027, Australia.
| | - Bing Gu
- Medical Technology School, Xuzhou Medical University, Xuzhou, Jiangsu Province, China; Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China.
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Khorami-Sarvestani S, Hanash SM, Fahrmann JF, León-Letelier RA, Katayama H. Glycosylation in cancer as a source of biomarkers. Expert Rev Proteomics 2024; 21:345-365. [PMID: 39376081 DOI: 10.1080/14789450.2024.2409224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/12/2024] [Accepted: 09/17/2024] [Indexed: 10/09/2024]
Abstract
INTRODUCTION Glycosylation, the process of glycan synthesis and attachment to target molecules, is a crucial and common post-translational modification (PTM) in mammalian cells. It affects the protein's hydrophilicity, charge, solubility, structure, localization, function, and protection from proteolysis. Aberrant glycosylation in proteins can reveal new detection and therapeutic Glyco-biomarkers, which help to improve accurate early diagnosis and personalized treatment. This review underscores the pivotal role of glycans and glycoproteins as a source of biomarkers in human diseases, particularly cancer. AREAS COVERED This review delves into the implications of glycosylation, shedding light on its intricate roles in cancer-related cellular processes influencing biomarkers. It is underpinned by a thorough examination of literature up to June 2024 in PubMed, Scopus, and Google Scholar; concentrating on the terms: (Glycosylation[Title/Abstract]) OR (Glycan[Title/Abstract]) OR (glycoproteomics[Title/Abstract]) OR (Proteoglycans[Title/Abstract]) OR (Glycomarkers[Title/Abstract]) AND (Cancer[Title/Abstract]) AND ((Diagno*[Title/Abstract]) OR (Progno*[Title/Abstract])). EXPERT OPINION Glyco-biomarkers enhance early cancer detection, allow early intervention, and improve patient prognoses. However, the abundance and complex dynamic glycan structure may make their scientific and clinical application difficult. This exploration of glycosylation signatures in cancer biomarkers can provide a detailed view of cancer etiology and instill hope in the potential of glycosylation to revolutionize cancer research.
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Affiliation(s)
- Sara Khorami-Sarvestani
- Department of Clinical Cancer Prevention, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Samir M Hanash
- Department of Clinical Cancer Prevention, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Johannes F Fahrmann
- Department of Clinical Cancer Prevention, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ricardo A León-Letelier
- Department of Clinical Cancer Prevention, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Hiroyuki Katayama
- Department of Clinical Cancer Prevention, the University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Jin X, Zhang W, Han Q, Li Q, Zong J, Li X, Wang C, Jiang H, Yu G, Li G. Serum-based Comprehensive N-Glycans Profiling Analysis in Different Gastric Disease Stages by Porous Graphitic Carbon Liquid Chromatography-Mass Spectrometry Associated With Potential Marker Discovery. In Vivo 2024; 38:147-159. [PMID: 38148046 PMCID: PMC10756461 DOI: 10.21873/invivo.13421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Revised: 10/24/2023] [Accepted: 10/30/2023] [Indexed: 12/28/2023]
Abstract
BACKGROUND/AIM N-glycans are potential serum biomarkers due to their aberrant structure and abundance alteration during disease progression. Few studies have been associated with relative quantitative N-glycans profiling during different gastric disease stages. In this study, we conducted an investigation on the profiling of N-glycans in patients with gastric disease, as well as in healthy controls. MATERIALS AND METHODS In this study, the porous graphitization carbon chromatography-high resolution Fourier transform mass spectrometry (PGC-FTMS) method was applied to assess comprehensive N-glycans profiling in patients at different stages of gastric disease, including gastritis, atrophic gastritis, gastric ulcer, gastric polyps, and gastric cancer. RESULTS A total of 45 N-glycans (relative abundance >0.1%) were detected, and 9 N-glycans were found to be potential biomarkers for gastric disease detection. Along with the progression of gastric disease, the abundance of sialylated N-glycans increased, while that of core-fucosylated N-glycans decreased. Multivariate statistical analysis demonstrated that N-glycans profiling between gastritis and healthy controls had significant differences. The characteristic N-glycans distinguished gastric cancer from healthy controls, which had strong clinical diagnostic value. CONCLUSION The relative quantitative profile of N-glycans in different gastric disease stages was revealed and serum N-glycans are proposed for distinguishing gastric disease stages in clinical application.
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Affiliation(s)
- Xin Jin
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China
| | - Weibin Zhang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China
| | - Qing Han
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China
| | - Qinying Li
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China
| | - Jinbao Zong
- The Affiliated Hospital of Qingdao University, Qingdao, P.R. China
| | - Xiaoyu Li
- The Affiliated Hospital of Qingdao University, Qingdao, P.R. China
| | - Chen Wang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China
| | - Hao Jiang
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China;
- Laboratory for Marine Drugs and Bioproducts, Laoshan Laboratory, Qingdao, P.R. China
| | - Guangli Yu
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China
- Laboratory for Marine Drugs and Bioproducts, Laoshan Laboratory, Qingdao, P.R. China
| | - Guoyun Li
- Key Laboratory of Marine Drugs, Ministry of Education, School of Medicine and Pharmacy, Shandong Key Laboratory of Glycoscience and Glycotechnology, Ocean University of China, Qingdao, P.R. China;
- Laboratory for Marine Drugs and Bioproducts, Laoshan Laboratory, Qingdao, P.R. China
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Sousa P, Silva L, Luís C, Câmara JS, Perestrelo R. MALDI-TOF MS: A Promising Analytical Approach to Cancer Diagnostics and Monitoring. SEPARATIONS 2023; 10:453. [DOI: 10.3390/separations10080453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025] Open
Abstract
Cancer remains the second most common cause of death after cardiovascular diseases, accounting for nearly 10 million deaths in 2020. Although the incidence of cancer increases considerably with age, the cancer burden can also be reduced and have a high chance of cure through early detection, appropriate treatment, and care of patients. The development of high-throughput analytical approaches, like matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), contributes to identifying a pool of proteins/peptides as putative biomarkers for the early detection, diagnosis, and tumor progression. The purpose of the current review is to present an updated outline of recent proteome/peptidome research to establish putative cancer biomarkers using MALDI-TOF MS and highlight the applicability of statistical analysis in the oncology field. The pros and cons of MALDI-TOF MS application on cancer diagnostics and monitoring will be discussed, as well as compared with tandem mass spectrometry (MS/MS)-based proteomics (e.g., liquid chromatography–tandem mass spectrometry). In addition, pre-analytical (e.g., sample quality control) and analytical (e.g., sample pre-treatment, instrumental analytical conditions) properties that influence the robustness of MALDI-TOF MS data will be also discussed.
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Affiliation(s)
- Patrícia Sousa
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal
| | - Laurentina Silva
- Hospital Dr. Nélio Mendonça, SESARAM, EPERAM—Serviço de Saúde da Região Autónoma da Madeira, Avenida Luís de CamõesK, 9004-514 Funchal, Portugal
| | - Catarina Luís
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal
| | - José S. Câmara
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal
- Departamento de Química, Faculdade de Ciências Exatas e Engenharia, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal
| | - Rosa Perestrelo
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9020-105 Funchal, Portugal
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Chang X, Obianwuna UE, Wang J, Zhang H, Qi G, Qiu K, Wu S. Glycosylated proteins with abnormal glycosylation changes are potential biomarkers for early diagnosis of breast cancer. Int J Biol Macromol 2023; 236:123855. [PMID: 36868337 DOI: 10.1016/j.ijbiomac.2023.123855] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Revised: 02/22/2023] [Accepted: 02/23/2023] [Indexed: 03/05/2023]
Abstract
Conventional cancer management relies on tumor type and stage for diagnosis and treatment, which leads to recurrence and metastasis and death in young women. Early detection of proteins in the serum aids diagnosis, progression, and clinical outcomes, possibly improving survival rate of breast cancer patients. In this review, we provided an insight into the influence of aberrant glycosylation on breast cancer development and progression. Examined literatures revealed that mechanisms underlying glycosylation moieties alteration could enhance early detection, monitoring, and therapeutic efficacy in breast cancer patients. This would serve as a guide for the development of new serum biomarkers with higher sensitivity and specificity, providing possible serological biomarkers for breast cancer diagnosis, progression, and treatment.
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Affiliation(s)
- Xinyu Chang
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Uchechukwu Edna Obianwuna
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Jing Wang
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Haijun Zhang
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Guanghai Qi
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
| | - Kai Qiu
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China.
| | - Shugeng Wu
- National Engineering Research Center of Biological Feed, Institute of Feed Research, Chinese Academy of Agricultural Sciences, Beijing 100081, China
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Harvey DJ. Analysis of carbohydrates and glycoconjugates by matrix-assisted laser desorption/ionization mass spectrometry: An update for 2017-2018. MASS SPECTROMETRY REVIEWS 2023; 42:227-431. [PMID: 34719822 DOI: 10.1002/mas.21721] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 07/26/2021] [Accepted: 07/26/2021] [Indexed: 06/13/2023]
Abstract
This review is the tenth update of the original article published in 1999 on the application of matrix-assisted laser desorption/ionization mass spectrometry (MALDI) mass spectrometry to the analysis of carbohydrates and glycoconjugates and brings coverage of the literature to the end of 2018. Also included are papers that describe methods appropriate to glycan and glycoprotein analysis by MALDI, such as sample preparation techniques, even though the ionization method is not MALDI. Topics covered in the first part of the review include general aspects such as theory of the MALDI process, new methods, matrices, derivatization, MALDI imaging, fragmentation and the use of arrays. The second part of the review is devoted to applications to various structural types such as oligo- and poly-saccharides, glycoproteins, glycolipids, glycosides, and biopharmaceuticals. Most of the applications are presented in tabular form. The third part of the review covers medical and industrial applications of the technique, studies of enzyme reactions, and applications to chemical synthesis. The reported work shows increasing use of combined new techniques such as ion mobility and highlights the impact that MALDI imaging is having across a range of diciplines. MALDI is still an ideal technique for carbohydrate analysis and advancements in the technique and the range of applications continue steady progress.
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Affiliation(s)
- David J Harvey
- Nuffield Department of Medicine, Target Discovery Institute, University of Oxford, Oxford, UK
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Construction of Stomach Cancer Lesion Detection Combined with Drug Therapy Based on Artificial Intelligence. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:1905437. [PMID: 36304779 PMCID: PMC9578819 DOI: 10.1155/2022/1905437] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Revised: 09/09/2022] [Accepted: 09/23/2022] [Indexed: 01/26/2023]
Abstract
The number of stomach cancer (SC) patients is increasing sharply every year, and gastroscope is a common method to check stomach-related diseases. A bulging lesion in the stomach is encountered during a gastroscopy. Due to the change in eating habits, the enhancement of health awareness, and the wide application of gastroscopy, the detection rate and cure rate of tumors have been significantly improved. This has certain clinical value for the early diagnosis and treatment of early SC. In this paper, based on the background of artificial intelligence, image segmentation technology is used to analyze and process the detection results of SC, so as to judge the effect of drug treatment. A total of 1408 gastric bulge lesions were investigated in 11023 patients during the one-year period 2019-2020. It also analyzed the age, lesion location, size, pathological type, and tumor detection results of 1408 patients. The experiment showed that among the 289 cases of submucosal bulging lesions, the detection rates of the young group, middle-aged group, and elderly group were 14.9% (43/289), 67.5% (195/289), and 17.6% (51/289), respectively. Among them, middle-aged people aged 41-65 have the highest detection rate. The incidence of gastric polyps was similar between different age groups. But with age, the rate of fundic gland polyps increases. The incidence of SC is not related to the age of the patient, but to its pathological type. The incidence of SC in middle-aged and elderly people is significantly higher than that in young people. SC is more common in the cardia, and gastrointestinal stromal tumors are most common with submucosal protrusion.
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Lyman DF, Bell A, Black A, Dingerdissen H, Cauley E, Gogate N, Liu D, Joseph A, Kahsay R, Crichton DJ, Mehta A, Mazumder R. Modeling and integration of N-glycan biomarkers in a comprehensive biomarker data model. Glycobiology 2022; 32:855-870. [PMID: 35925813 PMCID: PMC9487899 DOI: 10.1093/glycob/cwac046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/30/2022] [Accepted: 07/04/2022] [Indexed: 11/13/2022] Open
Abstract
Molecular biomarkers measure discrete components of biological processes that can contribute to disorders when impaired. Great interest exists in discovering early cancer biomarkers to improve outcomes. Biomarkers represented in a standardized data model, integrated with multi-omics data, may improve understanding and use of novel biomarkers such as glycans and glycoconjugates. Among altered components in tumorigenesis, N-glycans exhibit substantial biomarker potential, when analyzed with their protein carriers. However, such data are distributed across publications and databases of diverse formats, which hampers their use in research and clinical application. Mass spectrometry measures of fifty N-glycans, on seven serum proteins in liver disease, were integrated (as a panel) into a cancer biomarker data model, providing a unique identifier, standard nomenclature, links to glycan resources, and accession and ontology annotations to standard protein, gene, disease, and biomarker information. Data provenance was documented with a standardized FDA-supported BioCompute Object. Using the biomarker data model allows capture of granular information, such as glycans with different levels of abundance in cirrhosis, hepatocellular carcinoma, and transplant groups. Such representation in a standardized data model harmonizes glycomics data in a unified framework, making glycan-protein biomarker data exploration more available to investigators and to other data resources. The biomarker data model we describe can be used by researchers to describe their novel glycan and glycoconjugate biomarkers, can integrate N-glycan biomarker data with multi-source biomedical data, and can foster discovery and insight within a unified data framework for glycan biomarker representation thereby making the data FAIR (Findable, Accessible, Interoperable, Reusable) (https://www.go-fair.org/fair-principles/).
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Affiliation(s)
- Daniel F Lyman
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America
| | - Amanda Bell
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America
| | - Alyson Black
- The Department of Cell & Molecular Pharmacology, The Medical University of South Carolina, Charleston, SC, 29403, United States of America
| | - Hayley Dingerdissen
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America
| | - Edmund Cauley
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America.,The McCormick Genomic and Proteomic Center, The George Washington University, Washington, DC 20037, United States of America
| | - Nikhita Gogate
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America
| | - David Liu
- NASA Jet Propulsion Laboratory, Pasadena, CA 91109, United States of America
| | - Ashia Joseph
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America
| | - Robel Kahsay
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America
| | - Daniel J Crichton
- NASA Jet Propulsion Laboratory, Pasadena, CA 91109, United States of America
| | - Anand Mehta
- The Department of Cell & Molecular Pharmacology, The Medical University of South Carolina, Charleston, SC, 29403, United States of America
| | - Raja Mazumder
- The Department of Biochemistry & Molecular Medicine, The George Washington University Medical Center, Washington, DC 20037, United States of America.,The McCormick Genomic and Proteomic Center, The George Washington University, Washington, DC 20037, United States of America
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10
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Li P, Wang L, Guo R, Feng H, Ji Y, Lim SY, Ng BH, Laserna AKC, Khan S, Chen SM, Li SFY. Cross-identification of N-Glycans by CE-LIF using two capillary coatings and three labeling dyes. Talanta 2021; 239:123061. [PMID: 34809984 DOI: 10.1016/j.talanta.2021.123061] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2021] [Revised: 11/01/2021] [Accepted: 11/10/2021] [Indexed: 01/21/2023]
Abstract
Recombinant protein biopharmaceuticals comprise a significant portion of the current drug development landscape. The glycosylation profile of these proteins is a key quality parameter as it can affect their safety, efficacy, and stability. However, glycan analysis is challenging because of the complexity of their structures. To overcome this challenge in achieving accurate glycan identification, cross-identification of N-Glycans by CE-LIF method using two capillary coatings and three labeling dyes was developed in this work. This work explored whether complementary separation capabilities can be achieved using homemade polyvinyl alcohol (PVA) coating and commercial Guarant™ (Guarant) coating in the analysis of N-glycans. Similar separation profiles were observed using the two capillary coatings, and hence the N-glycan GU databases generated by these coatings were comparable and complementary. The performance of cross-validation by labeling with three fluorescent dyes indicated that low covariance of APTS and Turquoise™ labeling can be obtained, and hence these two labeling mechanisms provided better accuracy for the identification of glycans. Superior reproducibility with RSDs less than 1% for all target glycan standards was achieved by the internal standards (IS) method using maltodextrin ladders as additives in the separation buffer. The developed CE-LIF analysis method was applied to the identification of N-glycans in IgG samples.
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Affiliation(s)
- Pingjing Li
- Institute of Deep-sea Science and Engineering, Chinese Academy of Sciences, Sanya, Hainan, 572000, China; NUS Environmental Research Institute, National University of Singapore, T-Lab Building, 5A Engineering Drive 1, 117411, Singapore
| | - Lulu Wang
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore S117543
| | - Rui Guo
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore S117543
| | - Huatao Feng
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore S117543
| | - Ya Ji
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore S117543
| | - Si Ying Lim
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore S117543
| | - Bao Hui Ng
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore S117543
| | | | - Shaheer Khan
- Thermo Fisher Scientific, 180, Oyster Point Blvd, South San Francisco, CA, 94080, USA
| | - Shiaw-Min Chen
- Thermo Fisher Scientific, 180, Oyster Point Blvd, South San Francisco, CA, 94080, USA
| | - Sam Fong Yau Li
- Department of Chemistry, National University of Singapore, 3 Science Drive 3, Singapore S117543; NUS Environmental Research Institute, National University of Singapore, T-Lab Building, 5A Engineering Drive 1, 117411, Singapore.
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11
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Wu Y, Chen Y, Chen H, Yang C, Shen X, Deng C, Sun N, Wu H. Probing serum N-glycan patterns for rapid and precise detection of Crohn's disease. Chem Commun (Camb) 2021; 57:11362-11365. [PMID: 34643622 DOI: 10.1039/d1cc04699c] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Serum N-glycan patterns from 50 Crohn's disease (CD) patients and 50 healthy controls were acquired using a carbon matrix, from which eight N-glycans with significant difference were screened out to reveal remarkale performance for CD diagnosis. This research is expected to help future glycan-based disease detection not limited to CD.
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Affiliation(s)
- Yonglei Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China.
| | - Yijie Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China.
| | - Haolin Chen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China.
| | - Chenjie Yang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China.
| | - Xizhong Shen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China.
| | - Chunhui Deng
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China. .,Institutes of Biomedical Sciences, Fudan University, Shanghai 200433, China
| | - Nianrong Sun
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China.
| | - Hao Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, and Department of Chemistry, Fudan University, Shanghai 200032, China.
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12
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Differential Glycosylation Levels in Saliva from Patients with Lung or Breast Cancer: A Preliminary Assessment for Early Diagnostic Purposes. Metabolites 2021; 11:metabo11090566. [PMID: 34564382 PMCID: PMC8471868 DOI: 10.3390/metabo11090566] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/19/2021] [Accepted: 08/20/2021] [Indexed: 12/27/2022] Open
Abstract
Glycans play a fundamental role in several biological processes, such as cell-cell adhesion, signaling, and recognition. Similarly, abnormal glycosylation is involved in many pathological processes, among which include tumor growth and progression. Several highly glycosylated proteins found in blood are currently used in clinical practice as cancer biomarkers (e.g., CA125, PSA, and CA19-9). The development of novel non-invasive diagnostic procedures would greatly simplify the screening and discovery of pathologies at an early stage, thus also allowing for simpler treatment and a higher success rate. In this observational study carried out on 68 subjects diagnosed with either breast or lung cancer and 34 healthy volunteers, we hydrolyzed the glycoproteins in saliva and quantified the obtained free sugars (fucose, mannose, galactose, glucosamine, and galactosamine) by using high-performance anion-exchange chromatography with pulsed-amperometric detection (HPAEC-PAD). The glycosidic profiles were compared by using multivariate statistical analysis, showing differential glycosylation patterns among the three categories. Furthermore, Receiver Operating Characteristics (ROC) analysis allowed obtaining a reliable and minimally invasive protocol able to discriminate between healthy and pathological subjects.
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13
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Tikhonov A, Smoldovskaya O, Feyzkhanova G, Kushlinskii N, Rubina A. Glycan-specific antibodies as potential cancer biomarkers: a focus on microarray applications. Clin Chem Lab Med 2021; 58:1611-1622. [PMID: 32324152 DOI: 10.1515/cclm-2019-1161] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Accepted: 03/10/2020] [Indexed: 02/06/2023]
Abstract
Glycosylation is one of the most common posttranslational modifications of proteins and lipids. In the case of tumors, cell transformation accompanied by aberrant glycosylation results in the expression of tumor-associated glycans that promote tumor invasion. As part of the innate immunity, anti-glycan antibodies recognize tumor-associated glycans, and these antibodies can be present in the bloodstream in the early stages of cancer. Recently, anti-glycan antibody profiles have been of interest in various cancer studies. Novel advantages in the field of analytical techniques have simplified the analysis of anti-glycan antibodies and made it easier to have more comprehensive knowledge about their functions. One of the robust approaches for studying anti-glycan antibodies engages in microarray technology. The analysis of glycan microarrays can provide more expanded information to simultaneously specify or suggest the role of antibodies to a wide variety of glycans in the progression of different diseases, therefore making it possible to identify new biomarkers for diagnosing cancer and/or the state of the disease. Thus, in this review, we discuss antibodies to various glycans, their application for diagnosing cancer and one of the most promising tools for the investigation of these molecules, microarrays.
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Affiliation(s)
- Aleksei Tikhonov
- Laboratory of Biological Microchips, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Olga Smoldovskaya
- Laboratory of Biological Microchips, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Guzel Feyzkhanova
- Laboratory of Biological Microchips, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
| | - Nikolay Kushlinskii
- Laboratory of Clinical Biochemistry, Federal State Budgetary Institution «N.N. Blokhin National Medical Research Center of Oncology» оf the Ministry of Health of the Russian Federation, Moscow, Russia
| | - Alla Rubina
- Laboratory of Biological Microchips, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia
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14
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Pan Y, Zhang L, Zhang R, Han J, Qin W, Gu Y, Sha J, Xu X, Feng Y, Ren Z, Dai J, Huang B, Ren S, Gu J. Screening and diagnosis of colorectal cancer and advanced adenoma by Bionic Glycome method and machine learning. Am J Cancer Res 2021; 11:3002-3020. [PMID: 34249441 PMCID: PMC8263652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Accepted: 03/29/2021] [Indexed: 06/13/2023] Open
Abstract
Colorectal cancer (CRC), one of the major health problems worldwide, mostly develops from colorectal adenomas. Advanced adenomas are generally considered as precancerous lesions and patients are recommended to remove the adenomas. Screening for colorectal cancer is usually performed by fecal tests (FOBT or FIT) and colonoscopy, however, their benefits are limited by uptake and adherence. Most CRC develops from colorectal advanced adenomas, but there is currently a lack of effective noninvasive screening method for advanced adenomas. N-glycans in human serum hold the great potentials as biomarker for diagnosis of human cancers. Our aim was to discover blood-based markers for screening and diagnosis of advanced adenomas and CRC, and to ascertain their efficiency in classifying healthy controls, patients with advanced adenomas and CRC by incorporating machine learning techniques with reliable and simple quantitative method with "Bionic Glycome" as internal standard based on the high-throughput Matrix-assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS). The quantitative results showed that there is a positive correlation between multi-antennary, sialylated N-glycans and CRC progress, while bi-antennary core-fucosylated N-glycans are negatively correlated with CRC progress. Machine learning is a powerful classification tool, suitable for mining big data, especially the large amount of data generated by high-throughput technologies. Using the predictive model constructed by machine learning, we obtained the classification accuracy of 75% for classification of 189 samples including CRC, advanced adenomas and healthy controls, and the accuracy of 87% for detection of the disease group that required treatment, including CRC and advanced adenomas. To our delight, the model successfully applied to the prediction of 176 samples collected a few months later, and five samples were wrongly predicted in the disease group. Overall, this diagnostic model we constructed here has valuable potential in the clinical application of detecting advanced adenomas and colorectal cancer and could compensate for the limitations of the current screening methods for detection of CRC and advanced adenomas.
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Affiliation(s)
- Yiqing Pan
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Lei Zhang
- Institutes of Biomedical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Rongrong Zhang
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Jing Han
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Wenjun Qin
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
- Department of Cardiothoracic Surgery, Shanghai Children’s Hospital, Shanghai Jiao Tong UniversityNo. 355, Luding Road, Shanghai 200062, P. R. China
| | - Yong Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Jichen Sha
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Xiaoyan Xu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Yi Feng
- Department of Colorectal Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
- Department of General Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
| | - Zhipeng Ren
- Department of Colorectal Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
- Department of General Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
| | - Jiawen Dai
- Department of Colorectal Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
- Department of General Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
| | - Ben Huang
- Department of Colorectal Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
- Department of General Surgery, Shanghai East Hospital, Tongji UniversityShanghai 200120, P. R. China
| | - Shifang Ren
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
| | - Jianxin Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan UniversityShanghai 200032, P. R. China
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15
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Vickram A, Srikumar P, Srinivasan S, Jeyanthi P, Anbarasu K, Thanigaivel S, Nibedita D, Jenila Rani D, Rohini K. Seminal exosomes - An important biological marker for various disorders and syndrome in human reproduction. Saudi J Biol Sci 2021; 28:3607-3615. [PMID: 34121904 PMCID: PMC8176048 DOI: 10.1016/j.sjbs.2021.03.038] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2020] [Revised: 03/09/2021] [Accepted: 03/09/2021] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Exosomes are nano-sized membrane vesicles, secreted by different types of cells into the body's biological fluids. They are found in abundance in semen as compared to other fluids. Exosomes contain a cargo of lipid molecules, proteins, phospholipids, cholesterol, mRNAs, and miRNAs. Each molecule of seminal exosomes (SE) has a potential role in male reproduction for childbirth. Many potential candidates are available within the seminal exosomes that can be used as diagnostic markers for various diseases or syndromes associated with male reproduction. Also these seminal exospmes play a major role in female reproductive tract for effective fertilization. AIM The aim of this review is to focus on the advancement of human seminal exosomal research and its various properties. METHODS We used many databases like Scopus, Google scholar, NCBI-NLM and other sources to filter the articles of interest published in exosomes. We used phrases like "Exosomes in human semen", "Composition of exosomes in human semen" and other relevant words to filter the best articles. RESULTS Seminal exosomes play a major role in sperm functions like cell-to-cell communication, motility of the sperm cells, maintaining survival capacity for the sperm in the female reproductive tract and spermatogenesis. Also, seminal exosomes are used as a carrier for many regulatory elements using small RNA molecules. miRNAs of the seminal exosomes can be used as a diagnostic marker for prostate cancer instead of prostate specific antigen (PSA). Epididymosomes can be used as a biomarker for reproductive diseases and male infertility. CONCLUSION Seminal exosomes could be used as biological markers for various reproductive disorders, male infertility diagnosis, and it can be used in anti-retroviral research for the identification of novel therapeutics for HIV-1 infection and transmission.
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Affiliation(s)
- A.S. Vickram
- Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - P.S. Srikumar
- Unit of Psychiatry, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah,Malaysia
| | - S. Srinivasan
- Department of Biomedical Engineering, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Palanivelu Jeyanthi
- Department of Biotechnology, Vel Tech Rangarajan Dr. Sagunthala R&D Institute of Science and Technology, Chennai, Tamil Nadu, India
| | - K. Anbarasu
- Department of Bioinformatics, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - S. Thanigaivel
- Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Dey Nibedita
- Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - D. Jenila Rani
- Department of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Karunakaran Rohini
- Unit of Biochemistry, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah, Malaysia
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16
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Wu Y, Zhang N, Wu H, Sun N, Deng C. Magnetic porous carbon-dependent platform for the determination of N-glycans from urine exosomes. Mikrochim Acta 2021; 188:66. [PMID: 33543311 DOI: 10.1007/s00604-021-04728-x] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Accepted: 01/22/2021] [Indexed: 12/13/2022]
Abstract
A magnetic porous carbon-dependent platform is established to separate and determine N-glycans from urine exosomes of healthy people and patients with gastric cancer. The results of the comparison reveal that 6 N-glycans shared by the two groups are downregulated, most of which present core fucose or bisecting N-acetylglucosamine (GlcNAc) type. In addition, five shared N-glycans including two of sialic acid type are upregulated. These obvious differences indicate the close relationship between glycans and gastric cancer thus permitting early diagnosis. A magnetic porous carbon material (FeMPC) from MIL-101(Fe) was employed to separate and analyze N-glycans from urine exosomes of healthy people and patients with gastric cancer.
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Affiliation(s)
- Yonglei Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of Chemistry, Fudan University, Shanghai, 200433, China
| | - Ning Zhang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Department of Chemistry, Fudan University, Shanghai, 200433, China
| | - Hao Wu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
| | - Nianrong Sun
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
| | - Chunhui Deng
- Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Department of Chemistry, Fudan University, Shanghai, 200433, China.
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17
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Kori M, Aydin B, Gulfidan G, Beklen H, Kelesoglu N, Caliskan Iscan A, Turanli B, Erzik C, Karademir B, Arga KY. The Repertoire of Glycan Alterations and Glycoproteins in Human Cancers. OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY 2021; 25:139-168. [PMID: 33404348 DOI: 10.1089/omi.2020.0210] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Cancer as the leading cause of death worldwide has many issues that still need to be addressed. Since the alterations on the glycan compositions or/and structures (i.e., glycosylation, sialylation, and fucosylation) are common features of tumorigenesis, glycomics becomes an emerging field examining the structure and function of glycans. In the past, cancer studies heavily relied on genomics and transcriptomics with relatively little exploration of the glycan alterations and glycoprotein biomarkers among individuals and populations. Since glycosylation of proteins increases their structural complexity by several orders of magnitude, glycome studies resulted in highly dynamic biomarkers that can be evaluated for cancer diagnosis, prognosis, and therapy. Glycome not only integrates our genetic background with past and present environmental factors but also offers a promise of more efficient patient stratification compared with genetic variations. Therefore, studying glycans holds great potential for better diagnostic markers as well as developing more efficient treatment strategies in human cancers. While recent developments in glycomics and associated technologies now offer new possibilities to achieve a high-throughput profiling of glycan diversity, we aim to give an overview of the current status of glycan research and the potential applications of the glycans in the scope of the personalized medicine strategies for cancer.
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Affiliation(s)
- Medi Kori
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Busra Aydin
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Gizem Gulfidan
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Hande Beklen
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Nurdan Kelesoglu
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Ayşegul Caliskan Iscan
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey.,Department of Pharmacy, Istinye University, Istanbul, Turkey
| | - Beste Turanli
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
| | - Can Erzik
- Department of Medical Biology and School of Medicine, Marmara University, Istanbul, Turkey
| | - Betul Karademir
- Department of Biochemistry, School of Medicine, Marmara University, Istanbul, Turkey.,Genetic and Metabolic Diseases Research and Investigation Center, Marmara University, Istanbul, Turkey
| | - Kazim Yalcin Arga
- Department of Bioengineering, Faculty of Engineering, Marmara University, Istanbul, Turkey
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18
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Zhao J, Qin R, Chen H, Yang Y, Qin W, Han J, Wang X, Ren S, Sun Y, Gu J. A nomogram based on glycomic biomarkers in serum and clinicopathological characteristics for evaluating the risk of peritoneal metastasis in gastric cancer. Clin Proteomics 2020; 17:34. [PMID: 32968368 PMCID: PMC7501696 DOI: 10.1186/s12014-020-09297-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Accepted: 09/08/2020] [Indexed: 02/07/2023] Open
Abstract
Background Peritoneal metastasis (PM) in gastric cancer (GC) remains an untreatable disease, and is difficult to diagnose preoperatively. Here, we aim to establish a novel prediction model. Methods The clinicopathologic characteristics of a cohort that included 86 non-metastatic GC patients and 43 PMGC patients from Zhongshan Hospital were retrospectively analysed to identify PM associated variables. Additionally, mass spectrometry and glycomic analysis were applied in the same cohort to find glycomic biomarkers in serum for the diagnosis of PM. A nomogram was established based on the associations between potential risk variables and PM. Results Overexpression of 4 N-glycans (H6N5L1E1: m/z 2620.93; H5N5F1E2: m/z 2650.98; H6N5E2, m/z 2666.96; H6N5L1E2, m/z 2940.08); weight loss ≥ 5 kg; tumour size ≥ 3 cm; signet ring cell or mucinous adenocarcinoma histology type; poor differentiation; diffuse or mixed Lauren classification; increased CA19-9, CA125, and CA724 levels; decreased lymphocyte count, haemoglobin, albumin, and pre-albumin levels were identified to be associated with PM. A nomogram that integrated with five independent risk factors (weight loss ≥ 5 kg, CA19-9 ≥ 37 U/mL, CA125 ≥ 35 U/mL, lymphocyte count < 2.0 * 10 ~ 9/L, and H5N5F1E2 expression ≥ 0.0017) achieved a good performance for diagnosis (AUC: 0.892, 95% CI 0.829–0.954). When 160 was set as the cut-off threshold value, the proposed nomogram represented a perfectly discriminating power for both sensitivity (0.97) and specificity (0.88). Conclusions The nomogram achieved an individualized assessment of the risk of PM in GC patients; thus, the nomogram could be used to assist clinical decision-making before surgery.
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Affiliation(s)
- Junjie Zhao
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032 China
| | - Ruihuan Qin
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032 China.,Chinese Institute for Brain Research, Beijing, 102206 China
| | - Hao Chen
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032 China
| | - Yupeng Yang
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032 China
| | - Wenjun Qin
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032 China
| | - Jing Han
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032 China
| | - Xuefei Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032 China
| | - Shifang Ren
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032 China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032 China
| | - Jianxin Gu
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 138 Yixueyuan Road, Shanghai, 200032 China
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19
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Pérez AG, Andrade-Da-Costa J, De Souza WF, De Souza Ferreira M, Boroni M, De Oliveira IM, Freire-Neto CA, Fernandes PV, De Lanna CA, Souza-Santos PT, Morgado-Díaz JA, De-Freitas-Junior JCM. N‑glycosylation and receptor tyrosine kinase signaling affect claudin‑3 levels in colorectal cancer cells. Oncol Rep 2020; 44:1649-1661. [PMID: 32945502 PMCID: PMC7448416 DOI: 10.3892/or.2020.7727] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 07/14/2020] [Indexed: 12/14/2022] Open
Abstract
Changes in protein levels in different components of the apical junctional complex occur in colorectal cancer (CRC). Claudin-3 is one of the main constituents of tight junctions, and its overexpression can increase the paracellular flux of macromolecules, as well as the malignant potential of CRC cells. The aim of this study was to investigate the molecular mechanisms involved in the regulation of claudin-3 and its prognostic value in CRC. In silico evaluation in each of the CRC consensus molecular subtypes (CMSs) revealed that high expression levels of CLDN3 (gene encoding claudin-3) in CMS2 and CMS3 worsened the patients' long-term survival, whereas a decrease in claudin-3 levels concomitant with a reduction in phosphorylation levels of epidermal growth factor receptor (EGFR) and insulin-like growth factor 1 receptor (IGF1R) could be achieved by inhibiting N-glycan biosynthesis in CRC cells. We also observed that specific inactivation of these receptor tyrosine kinases (RTKs) led to a decrease in claudin-3 levels, and this regulation seems to be mediated by phospholipase C (PLC) and signal transducer and activator of transcription 3 (STAT3) in CRC cells. RTKs are modulated by their N-linked glycans, and inhibition of N-glycan biosynthesis decreased the claudin-3 levels; therefore, we evaluated the correlation between N-glycogenes and CLDN3 expression levels in each of the CRC molecular subtypes. The CMS1 (MSI immune) subtype concomitantly exhibited low expression levels of CLDN3 and N-glycogenes (MGAT5, ST6GAL1, and B3GNT8), whereas CMS2 (canonical) exhibited high gene expression levels of CLDN3 and N-glycogenes (ST6GAL1 and B3GNT8). A robust positive correlation was also observed between CLDN3 and B3GNT8 expression levels in all CMSs. These results support the hypothesis of a mechanism integrating RTK signaling and N-glycosylation for the regulation of claudin-3 levels in CRC, and they suggest that CLDN3 expression can be used to predict the prognosis of patients identified as CMS2 or CMS3.
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Affiliation(s)
- Amelia G Pérez
- Cellular and Molecular Oncobiology Program, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Jéssica Andrade-Da-Costa
- Cellular and Molecular Oncobiology Program, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Waldemir F De Souza
- Cellular and Molecular Oncobiology Program, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Michelle De Souza Ferreira
- Cellular and Molecular Oncobiology Program, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Mariana Boroni
- Bioinformatics and Computational Biology Laboratory, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Ivanir M De Oliveira
- Pathology Division, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Carlos A Freire-Neto
- Cellular and Molecular Oncobiology Program, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Priscila V Fernandes
- Pathology Division, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | - Cristóvão A De Lanna
- Bioinformatics and Computational Biology Laboratory, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
| | | | - José A Morgado-Díaz
- Cellular and Molecular Oncobiology Program, National Cancer Institute (INCA), Rio de Janeiro, RJ 20231‑050, Brazil
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Zhang W, Yang Z, Gao X, Wu Q. Advances in the discovery of novel biomarkers for cancer: spotlight on protein N-glycosylation. Biomark Med 2020; 14:1031-1045. [PMID: 32940073 DOI: 10.2217/bmm-2020-0185] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 05/21/2020] [Indexed: 02/06/2023] Open
Abstract
Progress on glycosylation and tumor markers has not been extensively reported. Glycosylation plays an important part in post-translational modification. Previous research on glycosylation-modified biomarkers has lagged behind due to insufficient understanding of glycosylation-related regulations. However, some new methods and ideas illustrated in recent research may provide new inspirations in the field. This article aims to review current advances in revealing relationship between tumors and abnormal N-glycosylation and discuss leading-edge applications of N-glycosylation in developing novel tumor biomarkers.
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Affiliation(s)
- Wenyao Zhang
- State Key Laboratory of Cancer Biology & National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 West Changle Road, Xi'an 710032, China
| | - Zhiping Yang
- State Key Laboratory of Cancer Biology & National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 West Changle Road, Xi'an 710032, China
| | - Xiaoliang Gao
- State Key Laboratory of Cancer Biology & National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 West Changle Road, Xi'an 710032, China
| | - Qiong Wu
- State Key Laboratory of Cancer Biology & National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 West Changle Road, Xi'an 710032, China
- Department of Clinical Nutrition, Xijing Hospital, Fourth Military Medical University, 127 West Changle Road, Xi'an 710032, China
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21
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Wang L, Yang L, Zhang Y, Lu H. Dual isotopic labeling combined with fluorous solid-phase extraction for simultaneous discovery of neutral/sialylated N-glycans as biomarkers for gastric cancer. Anal Chim Acta 2020; 1104:87-94. [DOI: 10.1016/j.aca.2020.01.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Revised: 12/23/2019] [Accepted: 01/01/2020] [Indexed: 12/11/2022]
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22
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Glycomics studies using sialic acid derivatization and mass spectrometry. Nat Rev Chem 2020; 4:229-242. [PMID: 37127981 DOI: 10.1038/s41570-020-0174-3] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/20/2020] [Indexed: 12/13/2022]
Abstract
Proteins can undergo glycosylation during and/or after translation to afford glycoconjugates, which are often secreted by a cell or populate cell surfaces. Changes in the glycan portion can have a strong influence on a glycoconjugate and are associated with a multitude of human pathologies. Of particular interest are sialylated glycoconjugates, which exist as constitutional isomers that differ in their linkages (α2,3, α2,6, α2,8 or α2,9) between sialic acids and their neighbouring monosaccharides. In general, mass spectrometry enables the rapid and sensitive characterization of glycosylation, but there are challenges specific to identifying and (relatively) quantifying sialic acid isomers. These challenges can be addressed using linkage-specific methodologies for sialic acid derivatization, after which mass spectrometry can enable product identification. This Review is concerned with the new and important derivatization approaches reported in the past decade, which have been implemented in various mass-spectrometry-glycomics workflows and have found clinical glycomics applications. The convenience and wide applicability of the approaches make them attractive for studies of sialylation in different types of glycoconjugate.
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Zhang D, Xie Q, Wang Q, Wang Y, Miao J, Li L, Zhang T, Cao X, Li Y. Mass spectrometry analysis reveals aberrant N-glycans in colorectal cancer tissues. Glycobiology 2019; 29:372-384. [PMID: 30698702 DOI: 10.1093/glycob/cwz005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Revised: 11/23/2018] [Accepted: 01/26/2019] [Indexed: 12/17/2022] Open
Abstract
Aberrant glycosylation is strongly correlated with the development of various cancers. Tumor-associated carbohydrate antigens, including N-glycans, are predominantly expressed on the tumor cell surface. Because the incidence of colorectal cancer is high in China, we investigated aberrant N-glycans from colorectal cancer tissues (CRC) in Chinese patients. By Linear ion trap quadrupole-electrospray ionization mass spectrometry, we performed glycomic assays on N-glycans obtained from solid CRC tissues and paired peritumoral tissues. In total, aberrant N-glycans were expressed in the colorectal tumor tissues. Specifically, seven bisecting structures (M/Z 9732+, 10602+, 10752+, 11622+, 11772+, 12642+, 13522+) decreased, M/Z 10552+ (two-antennae complex N-glycan) and M/Z 12792+ (three-antennae complex N-glycan) decreased, M/Z 10132+ and M/Z 11162+ (high-mannose N-glycan) increased, and M/Z 12282+ (bifucosylated N-glycan) increased. To evaluate the MS profile data, several statistical tools were applied, including student's t test, orthogonal partial least squares discriminant analysis and receiver operating characteristic curve. The measurement of the degree of bisecting N-glycans had an area under the curve value of 0.823. Interestingly, we observed that the bisecting N-glycans decreased with the tumor stages. This phenomenon was not found in esophageal squamous cell carcinoma, in which the bisecting N-glycans had no change. Thus, the expression of bisecting N-glycans may be an interesting point in the study of colorectal cancer.
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Affiliation(s)
- Dongmei Zhang
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, 199 Ren-Ai Road, SuZhou, Jiangsu Province, China
| | - Qing Xie
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, 199 Ren-Ai Road, SuZhou, Jiangsu Province, China
| | - Qian Wang
- Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Yanping Wang
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, 199 Ren-Ai Road, SuZhou, Jiangsu Province, China
| | - Jinsheng Miao
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, 199 Ren-Ai Road, SuZhou, Jiangsu Province, China
| | - Ling Li
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, 199 Ren-Ai Road, SuZhou, Jiangsu Province, China
| | - Tong Zhang
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, 199 Ren-Ai Road, SuZhou, Jiangsu Province, China
| | - Xiufeng Cao
- Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.,Taikang Xianlin Drum Tower Hospital School of Medicine, Nanjing University, Nanjing, Jiangsu Province, China
| | - Yunsen Li
- Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Science, Soochow University, 199 Ren-Ai Road, SuZhou, Jiangsu Province, China
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Mass spectrometry-based qualitative and quantitative N-glycomics: An update of 2017-2018. Anal Chim Acta 2019; 1091:1-22. [PMID: 31679562 DOI: 10.1016/j.aca.2019.10.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2019] [Revised: 10/04/2019] [Accepted: 10/05/2019] [Indexed: 12/14/2022]
Abstract
N-glycosylation is one of the most frequently occurring protein post-translational modifications (PTMs) with broad cellular, physiological and pathological relevance. Mass spectrometry-based N-glycomics has become the state-of-the-art instrumental analytical pipeline for sensitive, high-throughput and comprehensive characterization of N-glycans and N-glycomes. Improvement and new development of methods in N-glycan release, enrichment, derivatization, isotopic labeling, separation, ionization, MS, tandem MS and informatics accompany side-by-side wider and deeper application. This review provides a comprehensive update of mass spectrometry-based qualitative and quantitative N-glycomics in the years of 2017-2018.
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Keeley TS, Yang S, Lau E. The Diverse Contributions of Fucose Linkages in Cancer. Cancers (Basel) 2019; 11:E1241. [PMID: 31450600 PMCID: PMC6769556 DOI: 10.3390/cancers11091241] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Revised: 08/12/2019] [Accepted: 08/20/2019] [Indexed: 12/17/2022] Open
Abstract
Fucosylation is a post-translational modification of glycans, proteins, and lipids that is responsible for many biological processes. Fucose conjugation via α(1,2), α(1,3), α(1,4), α(1,6), and O'- linkages to glycans, and variations in fucosylation linkages, has important implications for cancer biology. This review focuses on the roles that fucosylation plays in cancer, specifically through modulation of cell surface proteins and signaling pathways. How L-fucose and serum fucosylation patterns might be used for future clinical diagnostic, prognostic, and therapeutic approaches will be discussed.
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Affiliation(s)
- Tyler S Keeley
- Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA
- University of South Florida Cancer Biology Graduate Program, Tampa, FL 33602, USA
- Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL 33602, USA
| | - Shengyu Yang
- Department of Cellular and Molecular Physiology, Penn State College of Medicine, Hershey, PA 17033, USA.
| | - Eric Lau
- Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL 33602, USA.
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Gebrehiwot AG, Melka DS, Kassaye YM, Gemechu T, Lako W, Hinou H, Nishimura SI. Exploring serum and immunoglobulin G N-glycome as diagnostic biomarkers for early detection of breast cancer in Ethiopian women. BMC Cancer 2019; 19:588. [PMID: 31208374 PMCID: PMC6580580 DOI: 10.1186/s12885-019-5817-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2018] [Accepted: 06/11/2019] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Alterations in protein glycosylation patterns have potentially been targeted for biomarker discovery in a wide range of diseases including cancer. Although there have been improvements in patient diagnosis and survival for breast cancer (BC), there is no clinically validated serum biomarker for its early diagnosis. Here, we profiled whole serum and purified Immunoglobulin G (IgG) fraction N-glycome towards identification of non-invasive glycan markers of BC. METHODS We employed a comprehensive glycomics approach by integrating glycoblotting-based glycan purification with MALDI-TOF/MS based quantitative analysis. Sera of BC patients belonging to stages I-IV and normal controls (NC) were collected from Ethiopian women during 2015-2016. IgG was purified by affinity chromatography using protein G spin plate and further subjected to glycoblotting for glycan release. Mass spectral data were further processed and evaluated rigorously, using various bioinformatics and statistical tools. RESULTS Out of 35 N-glycans that were significantly up-regulated in the sera of all BC patients compared to the NC, 17 complex type N-glycans showed profound expression abundance and diagnostic potential (AUC = 0.8-1) for the early stage (I and II) BC patients. Most of these glycans were core-fucosylated, multiply branched and sialylated structures, whose abundance has been strongly associated with greater invasive and metastatic potential of cancer. N-glycans quantified form IgG confirmed their abundance in BC patients, of which two core-fucosylated and agalactosylated glycans (m/z 1591, 1794) could specifically distinguish (AUC = 0.944 and 0.921, p ≤ 0.001) stage II patients from NC. Abundance of such structural features in IgG is associated with a decrease in its immunosuppressive potential towards tumor cells, which in part may correlate with the aggressive nature of BC commonly noticed in black population. CONCLUSIONS Our comprehensive study has addressed for the first time both whole serum and IgG N-glycosylation signatures of native black women suffering from BC and revealed novel glyco-biomarkers with marked overexpression and distinguishing ability at early stage patients. Further studies on direct identification of the intact glycoproteins using a glycoprteomics approach will provide a deeper understanding of specific biomarkers towards their clinical utility.
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Affiliation(s)
- Abrha G. Gebrehiwot
- Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021 Japan
| | - Daniel Seifu Melka
- Department of Biochemistry, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Yimenashu Mamo Kassaye
- Department of Biochemistry, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Tufa Gemechu
- Department of Pathology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Wajana Lako
- Department of Pathology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia
| | - Hiroshi Hinou
- Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021 Japan
| | - Shin-Ichiro Nishimura
- Faculty of Advanced Life Science and Graduate School of Life Science, Hokkaido University, N21, W11, Kita-ku, Sapporo, 001-0021 Japan
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Qin R, Yang Y, Qin W, Han J, Chen H, Zhao J, Zhao R, Li C, Gu Y, Pan Y, Wang X, Ren S, Sun Y, Gu J. The Value of Serum Immunoglobulin G Glycome in the Preoperative Discrimination of Peritoneal Metastasis from Advanced Gastric Cancer. J Cancer 2019; 10:2811-2821. [PMID: 31258789 PMCID: PMC6584920 DOI: 10.7150/jca.31380] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2018] [Accepted: 05/08/2019] [Indexed: 12/16/2022] Open
Abstract
Background: Peritoneal metastasis, associated with poor prognosis in gastric cancer, is difficult to discriminate from advanced gastric cancer preoperatively. However, operative diagnosis could bring both mental and physical trauma and economic burden for patients. Consequently, a non-invasive biomarker is necessary to reduce the burden of operative diagnosis and improve survival quality of patients. This study aims to elucidate the correlation between Immunoglobulin G (IgG) N-glycome and peritoneal metastasis and find potential biomarkers in preoperative discrimination of peritoneal metastasis from advanced gastric cancer based on the comprehensive sample set. Methods: A total of 373 gastric cancer patients were enrolled and randomly sorted into training cohort (n=249) and validation cohort (n=124). The IgG N-glycome composition was analyzed by ultra-performance liquid chromatography. Results: Twenty-four glycan peaks were directly detected and 15 traits based on the same structures were evaluated between peritoneal metastasis group and advanced gastric cancer group. Several differences in IgG glycosylation were found: sialylation and fucosylation were increased in peritoneal metastasis, while neutral glycosylation, monogalacosylation and bisecting GlcNAc were decreased. Based on the significant glycomics profile, a glyco-model composed of five glycan peaks (GP6, GP9, GP11, GP21 and GP23) was established with area under the receiver operating characteristic curve (AUC) value of 0.80 (training cohort) and 0.77 (validation cohort), which showed good potential in discriminating peritoneal metastasis from advanced gastric cancer. The diagnostic performance of this model was further validated in a combined cohort (AUC=0.79). Two patients with gastric cancer were selected to perform and demonstrate the usage of the diagnostic workflow. Conclusions: Here we firstly present IgG glycome profiles in a large number of preoperative peritoneal metastasis serums. The IgG glycan was highly associated with peritoneal metastasis. These findings enhance the understanding of peritoneal metastasis. Besides, our results suggested that the newly established glyco-model could be a reliable predictor of the presence of peritoneal metastasis in patients with advanced gastric cancer.
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Affiliation(s)
- Ruihuan Qin
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yupeng Yang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Wenjun Qin
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jing Han
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Hao Chen
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Junjie Zhao
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Ran Zhao
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
| | - Can Li
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yong Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yiqing Pan
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Xuefei Wang
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Shifang Ren
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yihong Sun
- Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jianxin Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
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Ciocan-Cartita CA, Jurj A, Buse M, Gulei D, Braicu C, Raduly L, Cojocneanu R, Pruteanu LL, Iuga CA, Coza O, Berindan-Neagoe I. The Relevance of Mass Spectrometry Analysis for Personalized Medicine through Its Successful Application in Cancer "Omics". Int J Mol Sci 2019; 20:ijms20102576. [PMID: 31130665 PMCID: PMC6567119 DOI: 10.3390/ijms20102576] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 05/21/2019] [Accepted: 05/24/2019] [Indexed: 01/06/2023] Open
Abstract
Mass spectrometry (MS) is an essential analytical technology on which the emerging omics domains; such as genomics; transcriptomics; proteomics and metabolomics; are based. This quantifiable technique allows for the identification of thousands of proteins from cell culture; bodily fluids or tissue using either global or targeted strategies; or detection of biologically active metabolites in ultra amounts. The routine performance of MS technology in the oncological field provides a better understanding of human diseases in terms of pathophysiology; prevention; diagnosis and treatment; as well as development of new biomarkers; drugs targets and therapies. In this review; we argue that the recent; successful advances in MS technologies towards cancer omics studies provides a strong rationale for its implementation in biomedicine as a whole.
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Affiliation(s)
- Cristina Alexandra Ciocan-Cartita
- MEDFUTURE -Research Center for Advanced Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy, 4-6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
| | - Ancuța Jurj
- Research Center for Functional Genomics, Biomedicine and Translational Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy.
| | - Mihail Buse
- MEDFUTURE -Research Center for Advanced Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy, 4-6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
| | - Diana Gulei
- MEDFUTURE -Research Center for Advanced Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy, 4-6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy.
| | - Lajos Raduly
- Research Center for Functional Genomics, Biomedicine and Translational Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy.
| | - Roxana Cojocneanu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy.
| | - Lavinia Lorena Pruteanu
- MEDFUTURE -Research Center for Advanced Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy, 4-6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
| | - Cristina Adela Iuga
- MEDFUTURE -Research Center for Advanced Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy, 4-6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
- Department of Pharmaceutical Analysis, Faculty of Pharmacy, "Iuliu Hațieganu" University of Medicine and Pharmacy, 6 Louis Pasteur Street, 400349 Cluj-Napoca.
| | - Ovidiu Coza
- Department of Oncology, "Iuliu Hațieganu" University of Medicine and Pharmacy, 34-36 Republicii Street, 400015 Cluj-Napoca, Romania.
- Department of Radiotherapy with High Energies and Brachytherapy, Oncology Institute "Prof. Dr. Ion Chiricuta", 34-36 Republicii Street, 400015 Cluj-Napoca.
| | - Ioana Berindan-Neagoe
- MEDFUTURE -Research Center for Advanced Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy, 4-6 Louis Pasteur Street, 400349 Cluj-Napoca, Romania.
- Research Center for Functional Genomics, Biomedicine and Translational Medicine," Iuliu Hațieganu" University of Medicine and Pharmacy.
- Department of Functional Genomics and Experimental Pathology, Ion Chiricuțǎ Oncology Institute, 34-36 Republicii Street, 400015 Cluj-Napoca.
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Necula L, Matei L, Dragu D, Neagu AI, Mambet C, Nedeianu S, Bleotu C, Diaconu CC, Chivu-Economescu M. Recent advances in gastric cancer early diagnosis. World J Gastroenterol 2019; 25:2029-2044. [PMID: 31114131 PMCID: PMC6506585 DOI: 10.3748/wjg.v25.i17.2029] [Citation(s) in RCA: 289] [Impact Index Per Article: 48.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2019] [Revised: 04/03/2019] [Accepted: 04/19/2019] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer (GC) remains an important cause of cancer death worldwide with a high mortality rate due to the fact that the majority of GC cases are diagnosed at an advanced stage when the prognosis is poor and the treatment options are limited. Unfortunately, the existing circulating biomarkers for GC diagnosis and prognosis display low sensitivity and specificity and the GC diagnosis is based only on the invasive procedures such as upper digestive endoscopy. There is a huge need for less invasive or non-invasive tests but also highly specific biomarkers in case of GC. Body fluids such as peripheral blood, urine or saliva, stomach wash/gastric juice could be a source of specific biomarkers, providing important data for screening and diagnosis in GC. This review summarized the recently discovered circulating molecules such as microRNAs, long non-coding RNAs, circular RNAs, which hold the promise to develop new strategies for early diagnosis of GC.
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Affiliation(s)
- Laura Necula
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
- Faculty of Medicine, Titu Maiorescu University, Bucharest 040441, Romania
| | - Lilia Matei
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Denisa Dragu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Ana I Neagu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Cristina Mambet
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Saviana Nedeianu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Coralia Bleotu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Carmen C Diaconu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
| | - Mihaela Chivu-Economescu
- Department of Cellular and Molecular Pathology, Stefan S. Nicolau Institute of Virology, Bucharest 030304, Romania
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Zhang Z, Westhrin M, Bondt A, Wuhrer M, Standal T, Holst S. Serum protein N-glycosylation changes in multiple myeloma. Biochim Biophys Acta Gen Subj 2019; 1863:960-970. [DOI: 10.1016/j.bbagen.2019.03.001] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2018] [Revised: 02/22/2019] [Accepted: 03/01/2019] [Indexed: 10/27/2022]
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Wang M, Zhu J, Lubman DM, Gao C. Aberrant glycosylation and cancer biomarker discovery: a promising and thorny journey. Clin Chem Lab Med 2019; 57:407-416. [PMID: 30138110 PMCID: PMC6785348 DOI: 10.1515/cclm-2018-0379] [Citation(s) in RCA: 123] [Impact Index Per Article: 20.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2018] [Accepted: 07/15/2018] [Indexed: 12/12/2022]
Abstract
Glycosylation is among the most important post-translational modifications for proteins and is of intrinsic complex character compared with DNAs and naked proteins. Indeed, over 50%-70% of proteins in circulation are glycosylated, and the "sweet attachments" have versatile structural and functional implications. Both the configuration and composition of the attached glycans affect the biological activities of consensus proteins significantly. Glycosylation is generated by complex biosynthetic pathways comprising hundreds of glycosyltransferases, glycosidases, transcriptional factors, transporters and the protein backbone. In addition, lack of direct genetic templates and glyco-specific antibodies such as those commonly used in DNA amplification and protein capture makes research on glycans and glycoproteins even more difficult, thus resulting in sparse knowledge on the pathophysiological implications of glycosylation. Fortunately, cutting-edge technologies have afforded new opportunities and approaches for investigating cancer-related glycosylation. Thus, glycans as well as aberrantly glycosylated protein-based cancer biomarkers have been increasingly recognized. This mini-review highlights the most recent developments in glyco-biomarker studies in an effort to discover clinically relevant cancer biomarkers using advanced analytical methodologies such as mass spectrometry, high-performance liquid chromatographic/ultra-performance liquid chromatography, capillary electrophoresis, and lectin-based technologies. Recent clinical-centered glycobiological studies focused on determining the regulatory mechanisms and the relation with diagnostics, prognostics and even therapeutics are also summarized. These studies indicate that glycomics is a treasure waiting to be mined where the growth of cancer-related glycomics and glycoproteomics is the next great challenge after genomics and proteomics.
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Affiliation(s)
- Mengmeng Wang
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, P.R. China
| | - Jianhui Zhu
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - David M. Lubman
- Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Chunfang Gao
- Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, P.R. China
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Zhong A, Qin R, Qin W, Han J, Gu Y, Zhou L, Zhang H, Ren S, Lu R, Guo L, Gu J. Diagnostic Significance of Serum IgG Galactosylation in CA19-9-Negative Pancreatic Carcinoma Patients. Front Oncol 2019; 9:114. [PMID: 30873386 PMCID: PMC6402387 DOI: 10.3389/fonc.2019.00114] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Accepted: 02/07/2019] [Indexed: 01/21/2023] Open
Abstract
Background: Although Carbohydrate antigen 19-9 (CA19-9) is considered clinically useful and informative for pancreatic carcinoma (PC), false positive results, and false negative results have restricted its clinical use. Especially missed or delayed diagnosis of PC patients with negative CA19-9 value limited the utility. To improve prognosis of PC patients, the discovery of reliable biomarkers to assist CA19-9 is desired. Serum IgG galactosylation based on our previous report was altered in PC patients comparing to healthy controls. The objective of this study was to explore the diagnostic significance of IgG galactosylation in assisting CA19-9 for PC in a comprehensive way. Methods: Serum IgG galactosylation profiles were analyzed by MALDI-MS in cohort 1 (n = 252) and cohort 2 in which all CA19-9 levels were negative (n = 133). In each cohort, not only healthy controls and PC patients but also benign pancreatic disease (BPD) patients were enrolled. Peaks were acquired by the software of MALDI-MS sample acquisition, followed by being processed and analyzed by the software of Progenesis MALDI. IgG Gal-ratio, which was calculated from the relative intensity of peaks G0, G1, and G2 according to the formula (G0/(G1+G2×2)), was employed as an index for indicating the distribution of IgG galactosylation. Results: The Gal-ratio was elevated in PC comparing with that in non-cancer group (healthy controls and BPD). The area under the receiver operating characteristic curve (AUC) of IgG Gal-ratio was higher than that of CA19-9 (0.912 vs. 0.814). The performance was further improved when Gal-ratio and CA19-9 were combined (AUC: 0.928). Meanwhile, Gal-ratio also had great diagnostic value with a sensitivity of 92.31% (AUC: 0.883) in detection of PC at early stage. Notably, IgG Gal-ratio has great sensitivity (90.63%) and specificity (76.81%) in CA19-9-negative PC patients. Conclusions: IgG Gal-ratio had a great performance in detection of PC and could be used to assist CA19-9 in improving diagnosis performance through early stage detection, differentiation from BPD, and PC diagnosis with CA19-9-negative level.
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Affiliation(s)
- Ailing Zhong
- Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ruihuan Qin
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Wenjun Qin
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Jing Han
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Yong Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Lei Zhou
- Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China
| | - Hongqin Zhang
- Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Shifang Ren
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Renquan Lu
- Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Lin Guo
- Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Jianxin Gu
- NHC Key Laboratory of Glycoconjugates Research, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
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Liyanage OT, Brantley MR, Calixte EI, Solouki T, Shuford KL, Gallagher ES. Characterization of Electrospray Ionization (ESI) Parameters on In-ESI Hydrogen/Deuterium Exchange of Carbohydrate-Metal Ion Adducts. JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY 2019; 30:235-247. [PMID: 30353291 DOI: 10.1007/s13361-018-2080-1] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/29/2018] [Accepted: 10/04/2018] [Indexed: 05/25/2023]
Abstract
The conformations of glycans are crucial for their biological functions. In-electrospray ionization (ESI) hydrogen/deuterium exchange-mass spectrometry (HDX-MS) is a promising technique for studying carbohydrate conformations since rapidly exchanging functional groups, e.g., hydroxyls, can be labeled on the timeframe of ESI. However, regular application of in-ESI HDX to characterize carbohydrates requires further analysis of the in-ESI HDX methodology. For instance, in this method, HDX occurs concurrently to the analyte transitioning from solution to gas-phase ions. Therefore, there is a possibility of sampling both gas-phase and solution-phase conformations of the analyte. Herein, we differentiate in-ESI HDX of metal-adducted carbohydrates from gas-phase HDX and illustrate that this method analyzes solvated species. We also systematically examine the effects of ESI parameters, including spray solvent composition, auxiliary gas flow rate, sheath gas flow rate, sample infusion rate, sample concentration, and spray voltage, and discuss their effects on in-ESI HDX. Further, we model the structural changes of a trisaccharide, melezitose, and its intramolecular and intermolecular hydrogen bonding in solvents with different compositions of methanol and water. These molecular dynamic simulations support our experimental results and illustrate how an individual ESI parameter can alter the conformations we sample by in-ESI HDX. In total, this work illustrates how the fundamental processes of ESI alter the magnitude of HDX for carbohydrates and suggest parameters that should be considered and/or optimized prior to performing experiments with this in-ESI HDX technique. Graphical Abstract ᅟ.
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Affiliation(s)
- O Tara Liyanage
- Department of Chemistry & Biochemistry, Baylor University, One Bear Place #97348, Waco, TX, 76798, USA
| | - Matthew R Brantley
- Department of Chemistry & Biochemistry, Baylor University, One Bear Place #97348, Waco, TX, 76798, USA
| | - Emvia I Calixte
- Department of Chemistry & Biochemistry, Baylor University, One Bear Place #97348, Waco, TX, 76798, USA
| | - Touradj Solouki
- Department of Chemistry & Biochemistry, Baylor University, One Bear Place #97348, Waco, TX, 76798, USA
| | - Kevin L Shuford
- Department of Chemistry & Biochemistry, Baylor University, One Bear Place #97348, Waco, TX, 76798, USA
| | - Elyssia S Gallagher
- Department of Chemistry & Biochemistry, Baylor University, One Bear Place #97348, Waco, TX, 76798, USA.
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Ribaldone DG, Simondi D, Petrini E, Astegiano M, Durazzo M. Non-invasive biomarkers for gastric cancer diagnosis: ready for prime time? MINERVA BIOTECNOL 2019; 31. [DOI: 10.23736/s1120-4826.18.02463-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
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35
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Peng W, Zhao J, Dong X, Banazadeh A, Huang Y, Hussien A, Mechref Y. Clinical application of quantitative glycomics. Expert Rev Proteomics 2018; 15:1007-1031. [PMID: 30380947 PMCID: PMC6647030 DOI: 10.1080/14789450.2018.1543594] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Aberrant glycosylation has been associated with many diseases. Decades of research activities have reported many reliable glycan biomarkers of different diseases which enable effective disease diagnostics and prognostics. However, none of the glycan markers have been approved for clinical diagnosis. Thus, a review of these studies is needed to guide the successful clinical translation. Area covered: In this review, we describe and discuss advances in analytical methods enabling clinical glycan biomarker discovery, focusing only on studies of released glycans. This review also summarizes the different glycobiomarkers identified for cancers, Alzheimer's disease, diabetes, hepatitis B and C, and other diseases. Expert commentary: Along with the development of techniques in quantitative glycomics, more glycans or glycan patterns have been reported as better potential biomarkers of different diseases and proved to have greater diagnostic/diagnostic sensitivity and specificity than existing markers. However, to successfully apply glycan markers in clinical diagnosis, more studies and verifications on large biological cohorts need to be performed. In addition, faster and more efficient glycomic strategies need to be developed to shorten the turnaround time. Thus, glycan biomarkers have an immense chance to be used in clinical prognosis and diagnosis of many diseases in the near future.
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Affiliation(s)
- Wenjing Peng
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, United States
| | - Jingfu Zhao
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, United States
| | - Xue Dong
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, United States
| | - Alireza Banazadeh
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, United States
| | - Yifan Huang
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, United States
| | - Ahmed Hussien
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, United States
- Department of Biotechnology, Institute of Graduate Studies and Research, University of Alexandria, Alexandria, 21526, Egypt
| | - Yehia Mechref
- Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas, 79409, United States
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36
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Ruhaak LR, Xu G, Li Q, Goonatilleke E, Lebrilla CB. Mass Spectrometry Approaches to Glycomic and Glycoproteomic Analyses. Chem Rev 2018; 118:7886-7930. [PMID: 29553244 PMCID: PMC7757723 DOI: 10.1021/acs.chemrev.7b00732] [Citation(s) in RCA: 284] [Impact Index Per Article: 40.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Glycomic and glycoproteomic analyses involve the characterization of oligosaccharides (glycans) conjugated to proteins. Glycans are produced through a complicated nontemplate driven process involving the competition of enzymes that extend the nascent chain. The large diversity of structures, the variations in polarity of the individual saccharide residues, and the poor ionization efficiencies of glycans all conspire to make the analysis arguably much more difficult than any other biopolymer. Furthermore, the large number of glycoforms associated with a specific protein site makes it more difficult to characterize than any post-translational modification. Nonetheless, there have been significant progress, and advanced separation and mass spectrometry methods have been at its center and the main reason for the progress. While glycomic and glycoproteomic analyses are still typically available only through highly specialized laboratories, new software and workflow is making it more accessible. This review focuses on the role of mass spectrometry and separation methods in advancing glycomic and glycoproteomic analyses. It describes the current state of the field and progress toward making it more available to the larger scientific community.
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Affiliation(s)
- L. Renee Ruhaak
- Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
| | - Gege Xu
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, United States
| | - Qiongyu Li
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, United States
| | - Elisha Goonatilleke
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, United States
| | - Carlito B. Lebrilla
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, California 95616, United States
- Department of Biochemistry and Molecular Medicine, University of California, Davis, Davis, California 95616, United States
- Foods for Health Institute, University of California, Davis, Davis, California 95616, United States
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37
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Franceschi C, Garagnani P, Morsiani C, Conte M, Santoro A, Grignolio A, Monti D, Capri M, Salvioli S. The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front Med (Lausanne) 2018; 5:61. [PMID: 29662881 PMCID: PMC5890129 DOI: 10.3389/fmed.2018.00061] [Citation(s) in RCA: 552] [Impact Index Per Article: 78.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 02/20/2018] [Indexed: 12/11/2022] Open
Abstract
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.
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Affiliation(s)
- Claudio Franceschi
- Institute of Neurological Sciences, University of Bologna, Bellaria Hospital, Bologna, Italy
| | - Paolo Garagnani
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet at Huddinge University Hospital, Stockholm, Sweden.,Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy.,CNR Institute of Molecular Genetics, Unit of Bologna, Bologna, Italy
| | - Cristina Morsiani
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Maria Conte
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Aurelia Santoro
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy
| | - Andrea Grignolio
- Unit and Museum of History of Medicine, Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy
| | - Daniela Monti
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy
| | - Miriam Capri
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy
| | - Stefano Salvioli
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Interdepartmental Center "L. Galvani" (CIG), University of Bologna, Bologna, Italy
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38
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Qin W, Pei H, Qin R, Zhao R, Han J, Zhang Z, Dong K, Ren S, Gu J. Alteration of Serum IgG Galactosylation as a Potential Biomarker for Diagnosis of Neuroblastoma. J Cancer 2018; 9:906-913. [PMID: 29581769 PMCID: PMC5868155 DOI: 10.7150/jca.22014] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Accepted: 02/06/2018] [Indexed: 12/18/2022] Open
Abstract
Background: Neuroblastoma (NB) is the most frequent pediatric malignant neoplasm that originates from embryonic neural crest cells. Urinary catecholamines in 24-h urine are most commonly analyzed for the diagnosis of neuroblastoma at good sensitivity; however, it is challenging to collect 24-h urine samples in a pediatric population. Therefore, development of more rapid, non-invasive and cost-effective tools for the diagnosis of NB remains needed. Serum immunoglobulin G (IgG) galactosylation have been found highly associated with adult cancers in our previous study. Methods: To explore the potential use of serum IgG galactosylation in aiding diagnosis of neuroblastoma, serum IgG galactosylation profiles of 26 neuroblastoma cases and 30 age-matched non-malignant controls were analyzed by MALDI MS. The alteration of IgG galactosylation in neuroblastoma patients was measured by a Gal-ratio formula: G0/(G1+G2×2), calculating the relative intensities of agalactosylated N-glycan (G0) vs mono-galactosyl N-glycan (G1) and digalactosyl N-glycan (G2). Results: The results showed that IgG Gal-ratios were significantly higher in neuroblastoma cases compared with non-malignant controls (p=5.0×10-4). And the Gal-ratio data generated sensitivity and specificity of 84.62% and 60.00%, combined with an AUC (area under the curve) of 0.80. Conclusions: The analysis of serum IgG galactosylation distribution may play a suggestive role for neuroblastoma diagnosis, or serve as a potential biomarker for NB diagnosis.
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Affiliation(s)
- Wenjun Qin
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Hao Pei
- Department of Anesthesiology, Children's Hospital, Fudan University, Shanghai 201102, China
| | - Ruihuan Qin
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Ran Zhao
- Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200090, China
| | - Jing Han
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Zejian Zhang
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Kuiran Dong
- Department of Oncology, Children's Hospital, Fudan University, Shanghai 201102, China
| | - Shifang Ren
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
| | - Jianxin Gu
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
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39
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Kailemia MJ, Xu G, Wong M, Li Q, Goonatilleke E, Leon F, Lebrilla CB. Recent Advances in the Mass Spectrometry Methods for Glycomics and Cancer. Anal Chem 2018; 90:208-224. [PMID: 29049885 PMCID: PMC6200424 DOI: 10.1021/acs.analchem.7b04202] [Citation(s) in RCA: 61] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Affiliation(s)
- Muchena J. Kailemia
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- These authors contributed equally to this work
| | - Gege Xu
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- These authors contributed equally to this work
| | - Maurice Wong
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - Qiongyu Li
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - Elisha Goonatilleke
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - Frank Leon
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
| | - Carlito B. Lebrilla
- Department of Chemistry, University of California, Davis, One Shields Avenue, Davis, CA 95616, United States
- Department of Biochemistry and Molecular Medicine, University of California, Davis, CA 95616, USA
- Foods for Health Institute, University of California, Davis, CA 95616, USA
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