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1
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Peng H, Sun L, Zhao J, Cui G. Electrochemical detection of circulating-free DNA methylation: A new indicator for early cancer screening. Talanta 2025; 292:127925. [PMID: 40081249 DOI: 10.1016/j.talanta.2025.127925] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2024] [Revised: 01/23/2025] [Accepted: 03/10/2025] [Indexed: 03/15/2025]
Abstract
This study introduces a novel electrochemical approach for detecting circulating-free DNA (cfDNA) by leveraging distinct methylation patterns characteristic of cfDNA from healthy controls and cancer patients. Our findings reveal that cfDNA from cancer patients exhibits a unique affinity for gold surfaces due to abnormal methylation, which enables its electrochemical differentiation. By using square wave voltammetry (SWV) with optimized parameters, we achieved high sensitivity (0.89) and specificity (0.73) in distinguishing cfDNA from healthy controls and cancer patients. Clinical trials demonstrated the effectiveness of this method, surpassing conventional tumor markers in early cancer screening. SEPTIN9 (SEPT9) methylation is used as an example to demonstrate the generalizability of our method for analyzing DNA methylation changes, which can subsequently be applied to identify the presence of cancer.This approach offers notable advantages, including simplicity, rapid response, and cost-effectiveness. While the current methodology is primarily suited for detecting the presence of cancer, its potential for prognostic and diagnostic applications warrants further investigation.
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Affiliation(s)
- Han Peng
- School of Mechanical and Automotive Engineering, South China University of Technology, Guangzhou, 510640, PR China.
| | - Liyue Sun
- Department of Health Management Centre, Zhongshan Hospital, Fudan University, Shanghai, 200032, PR China.
| | - Jie Zhao
- School of Mechanical and Automotive Engineering, South China University of Technology, Guangzhou, 510640, PR China.
| | - Guofeng Cui
- School of Chemistry, Sun Yat-Sen University, Guangzhou, 510275, PR China.
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2
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Jiang X, Tao L, Cao S, Xu Z, Zheng S, Zhang H, Xu X, Qu X, Liu X, Yu J, Chen X, Wu J, Liang X. Porous Silicon Particle-Assisted Mass Spectrometry Technology Unlocks Serum Metabolic Fingerprints in the Progression From Chronic Hepatitis B to Hepatocellular Carcinoma. ACS APPLIED MATERIALS & INTERFACES 2025; 17:5893-5908. [PMID: 39812132 DOI: 10.1021/acsami.4c17563] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/16/2025]
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy and generally develops from liver cirrhosis (LC), which is primarily caused by the chronic hepatitis B (CHB) virus. Reliable liquid biopsy methods for HCC screening in high-risk populations are urgently needed. Here, we establish a porous silicon-assisted laser desorption ionization mass spectrometry (PSALDI-MS) technology to profile metabolite information hidden in human serum in a high throughput manner. Serum metabolites can be captured in the pore channel of APTES-modified porous silicon (pSi) particles and well-preserved during storage or transportation. Furthermore, serum metabolites captured in the APTES-pSi particles can be directly detected on the LDI-MS without the addition of an organic matrix, thus greatly accelerating the acquisition of metabolic fingerprints of serum samples. The PSALDI-MS displays the capability of high throughput (5 min per 96 samples), high reproducibility (coefficient of variation <15%), high sensitivity (LOD ∼ 1 pmol), and high tolerance to background salt and proteins. In a multicenter cohort study, 1433 subjects including healthy controls (HC), CHB, LC, and HCC volunteers were enrolled and nontargeted serum metabolomic analysis was performed on the PSALDI-MS platform. After the selection of feature metabolites, a stepwise diagnostic model for the classification of different liver disease stages was constructed by the machine learning algorithm. In external testing, the accuracy of 91.2% for HC, 71.4% for CHB, 70.0% for LC, and 95.3% for HCC was achieved by chemometrics. Preliminary studies indicated that the diagnostic model constructed from serum metabolic fingerprint also displays good predictive performance in a prospective observation. We believe that the combination of PSALDI-MS technology and machine learning may serve as an efficient tool in clinical practice.
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Affiliation(s)
- Xinrong Jiang
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
| | - Liye Tao
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
- Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
| | - Shuo Cao
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Zhengao Xu
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
- Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
| | - Shuang Zheng
- Taizhou First People's Hospital, Taizhou, Zhejiang 318020, China
| | - Huafang Zhang
- Wuyi First People's Hospital, Jinhua, Zhejiang 321200, China
| | - Xinran Xu
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Xuetong Qu
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Xingyue Liu
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310058, China
| | - Jiekai Yu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China
| | - Xiaoming Chen
- Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
- Well-healthcare Technologies Co., Hangzhou, Zhejiang 310051, China
| | - Jianmin Wu
- Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310058, China
- Children's Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China
| | - Xiao Liang
- Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
- Zhejiang Key Laboratory of Multi-omics Precision Diagnosis and Treatment of Liver Diseases, Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, China
- School of medicine, Shaoxing University, Shaoxing, Zhejiang 312000, China
- School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, Zhejiang 310000, China
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3
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Shi D, Grey AC, Guo G. An isotopically-labelled temporal mass spectrometry imaging data analysis workflow to reveal glucose spatial metabolism patterns in bovine lens tissue. Sci Rep 2024; 14:18843. [PMID: 39138264 PMCID: PMC11322647 DOI: 10.1038/s41598-024-69507-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 08/06/2024] [Indexed: 08/15/2024] Open
Abstract
Application of stable isotopically labelled (SIL) molecules in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) over a series of time points allows the temporal and spatial dynamics of biochemical reactions to be tracked in a biological system. However, these large kinetic MSI datasets and the inherent variability of biological replicates presents significant challenges to the rapid analysis of the data. In addition, manual annotation of downstream SIL metabolites involves human input to carefully analyse the data based on prior knowledge and personal expertise. To overcome these challenges to the analysis of spatiotemporal MALDI-MSI data and improve the efficiency of SIL metabolite identification, a bioinformatics pipeline has been developed and demonstrated by analysing normal bovine lens glucose metabolism as a model system. The pipeline consists of spatial alignment to mitigate the impact of sample variability and ensure spatial comparability of the temporal data, dimensionality reduction to rapidly map regional metabolic distinctions within the tissue, and metabolite annotation coupled with pathway enrichment modules to summarise and display the metabolic pathways induced by the treatment. This pipeline will be valuable for the spatial metabolomics community to analyse kinetic MALDI-MSI datasets, enabling rapid characterisation of spatio-temporal metabolic patterns from tissues of interest.
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Affiliation(s)
- Dingchang Shi
- Department of Physiology, School of Medical Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand
| | - Angus C Grey
- Department of Physiology, School of Medical Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand.
| | - George Guo
- Department of Physiology, School of Medical Sciences, University of Auckland, 85 Park Rd, Grafton, Auckland, 1023, New Zealand
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4
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Wilk SS, Michalak K, Owczarek EP, Winiarczyk S, Zabielska-Koczywąs KA. Proteomic Analyses Reveal the Role of Alpha-2-Macroglobulin in Canine Osteosarcoma Cell Migration. Int J Mol Sci 2024; 25:3989. [PMID: 38612805 PMCID: PMC11011979 DOI: 10.3390/ijms25073989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2024] [Revised: 03/25/2024] [Accepted: 03/29/2024] [Indexed: 04/14/2024] Open
Abstract
Canine osteosarcoma (OSA) is an aggressive bone neoplasia with high metastatic potential. Metastasis is the main cause of death associated with OSA, and there is no current treatment available for metastatic disease. Proteomic analyses, including matrix-assisted laser desorption/ionisation-time of flight mass spectrometry (MALDI TOF/TOF MS), are widely used to select molecular targets and identify proteins that may play a key role in primary tumours and at various steps of the metastatic cascade. The main aim of this study was to identify proteins differently expressed in canine OSA cell lines with different malignancy phenotypes (OSCA-8 and OSCA-32) compared to canine osteoblasts (CnOb). The intermediate aim of the study was to compare canine OSA cell migration capacity and assess its correlation with the malignancy phenotypes of each cell line. Using MALDI-TOF/TOF MS analyses, we identified eight proteins that were significantly differentially expressed (p ≤ 0.05) in canine OSA cell lines compared to CnOb: cilia- and flagella-associated protein 298 (CFAP298), general transcription factor II-I (GTF2I), mirror-image polydactyly gene 1 protein (MIPOL1), alpha-2 macroglobulin (A2M), phosphoglycerate mutase 1 (PGAM1), ubiquitin (UB2L6), ectodysplasin-A receptor-associated adapter protein (EDARADD), and leucine-rich-repeat-containing protein 72 (LRRC72). Using the Simple Western technique, we confirmed high A2M expression in CnOb compared to OSCA-8 and OSCA-32 cell lines (with intermediate and low A2M expression, respectively). Then, we confirmed the role of A2M in cancer cell migration by demonstrating significantly inhibited OSA cell migration by treatment with A2M (both at 10 and 30 mM concentrations after 12 and 24 h) in a wound-healing assay. This study may be the first report indicating A2M's role in OSA cell metastasis; however, further in vitro and in vivo studies are needed to confirm its possible role as an anti-metastatic agent in this malignancy.
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Affiliation(s)
- Sylwia S. Wilk
- Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-787 Warsaw, Poland; (S.S.W.); (E.P.O.)
| | - Katarzyna Michalak
- Department of Epizootiology and Clinic of Infectious Diseases, University of Life Sciences, Głęboka 30, 20-612 Lublin, Poland; (K.M.); (S.W.)
| | - Ewelina P. Owczarek
- Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-787 Warsaw, Poland; (S.S.W.); (E.P.O.)
- Laboratory of RNA Biology, International Institute of Molecular and Cell Biology in Warsaw, 4 Ks. Trojdena, 02-109 Warsaw, Poland
| | - Stanisław Winiarczyk
- Department of Epizootiology and Clinic of Infectious Diseases, University of Life Sciences, Głęboka 30, 20-612 Lublin, Poland; (K.M.); (S.W.)
- National Veterinary Research Institute, Aleja Partyzantów 5, 24-100 Puławy, Poland
| | - Katarzyna A. Zabielska-Koczywąs
- Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, Nowoursynowska 159c, 02-787 Warsaw, Poland; (S.S.W.); (E.P.O.)
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5
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Kralova K, Vrtelka O, Fouskova M, Smirnova TA, Michalkova L, Hribek P, Urbanek P, Kuckova S, Setnicka V. Comprehensive spectroscopic, metabolomic, and proteomic liquid biopsy in the diagnostics of hepatocellular carcinoma. Talanta 2024; 270:125527. [PMID: 38134814 DOI: 10.1016/j.talanta.2023.125527] [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: 07/15/2023] [Revised: 11/30/2023] [Accepted: 12/04/2023] [Indexed: 12/24/2023]
Abstract
Liquid biopsy is a very topical issue in clinical diagnostics research nowadays. In this study, we explored and compared various analytical approaches to blood plasma analysis. Finally, we proposed a comprehensive procedure, which, thanks to the utilization of multiple analytical techniques, allowed the targeting of various biomolecules in blood plasma reflecting diverse biological processes underlying disease development. The potential of such an approach, combining proteomics, metabolomics, and vibrational spectroscopy along with preceding blood plasma fractionation, was demonstrated on blood plasma samples of patients suffering from hepatocellular carcinoma in cirrhotic terrain (n = 20) and control subjects with liver cirrhosis (n = 20) as well as healthy subjects (n = 20). Most of the applied methods allowed the classification of the samples with an accuracy exceeding 80.0 % and therefore have the potential to be used as a stand-alone method in clinical diagnostics. Moreover, a final panel of 48 variables obtained by a combination of the utilized analytical methods enabled the discrimination of the hepatocellular carcinoma samples from cirrhosis with 94.3 % cross-validated accuracy. Thus, this study, although limited by the cohort size, clearly demonstrated the benefit of the multimethod approach in clinical diagnosis.
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Affiliation(s)
- Katerina Kralova
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technicka 5, 166 28, Prague 6, Czech Republic
| | - Ondrej Vrtelka
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technicka 5, 166 28, Prague 6, Czech Republic
| | - Marketa Fouskova
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technicka 5, 166 28, Prague 6, Czech Republic
| | - Tatiana Anatolievna Smirnova
- Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology, Prague, Technicka 5, 166 28, Prague 6, Czech Republic
| | - Lenka Michalkova
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technicka 5, 166 28, Prague 6, Czech Republic; Department of Analytical Chemistry, Institute of Chemical Process Fundamentals of the CAS, Rozvojova 135, 165 02, Prague 6, Czech Republic
| | - Petr Hribek
- Military University Hospital Prague, Department of Medicine 1st Faculty of Medicine Charles University and Military University Hospital Prague, U Vojenske Nemocnice 1200, 169 02, Prague 6, Czech Republic; Department of Internal Medicine, Faculty of Military Health Sciences in Hradec Kralove, University of Defense, Trebesska 1575, 500 01, Hradec Kralove, Czech Republic
| | - Petr Urbanek
- Military University Hospital Prague, Department of Medicine 1st Faculty of Medicine Charles University and Military University Hospital Prague, U Vojenske Nemocnice 1200, 169 02, Prague 6, Czech Republic
| | - Stepanka Kuckova
- Department of Biochemistry and Microbiology, Faculty of Food and Biochemical Technology, University of Chemistry and Technology, Prague, Technicka 5, 166 28, Prague 6, Czech Republic
| | - Vladimir Setnicka
- Department of Analytical Chemistry, Faculty of Chemical Engineering, University of Chemistry and Technology, Prague, Technicka 5, 166 28, Prague 6, Czech Republic.
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6
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Gobena S, Admassu B, Kinde MZ, Gessese AT. Proteomics and Its Current Application in Biomedical Area: Concise Review. ScientificWorldJournal 2024; 2024:4454744. [PMID: 38404932 PMCID: PMC10894052 DOI: 10.1155/2024/4454744] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 02/09/2024] [Accepted: 02/13/2024] [Indexed: 02/27/2024] Open
Abstract
Biomedical researchers tirelessly seek cutting-edge technologies to advance disease diagnosis, drug discovery, and therapeutic interventions, all aimed at enhancing human and animal well-being. Within this realm, proteomics stands out as a pivotal technology, focusing on extensive studies of protein composition, structure, function, and interactions. Proteomics, with its subdivisions of expression, structural, and functional proteomics, plays a crucial role in unraveling the complexities of biological systems. Various sophisticated techniques are employed in proteomics, including polyacrylamide gel electrophoresis, mass spectrometry analysis, NMR spectroscopy, protein microarray, X-ray crystallography, and Edman sequencing. These methods collectively contribute to the comprehensive understanding of proteins and their roles in health and disease. In the biomedical field, proteomics finds widespread application in cancer research and diagnosis, stem cell studies, and the diagnosis and research of both infectious and noninfectious diseases. In addition, it plays a pivotal role in drug discovery and the emerging frontier of personalized medicine. The versatility of proteomics allows researchers to delve into the intricacies of molecular mechanisms, paving the way for innovative therapeutic approaches. As infectious and noninfectious diseases continue to emerge and the field of biomedical research expands, the significance of proteomics becomes increasingly evident. Keeping abreast of the latest developments in proteomics applications becomes paramount for the development of therapeutics, translational research, and study of diverse diseases. This review aims to provide a comprehensive overview of proteomics, offering a concise outline of its current applications in the biomedical domain. By doing so, it seeks to contribute to the understanding and advancement of proteomics, emphasizing its pivotal role in shaping the future of biomedical research and therapeutic interventions.
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Affiliation(s)
- Semira Gobena
- College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia
| | - Bemrew Admassu
- Department of Veterinary Biomedical Sciences, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia
| | - Mebrie Zemene Kinde
- Department of Veterinary Biomedical Sciences, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia
| | - Abebe Tesfaye Gessese
- Department of Veterinary Biomedical Sciences, College of Veterinary Medicine and Animal Sciences, University of Gondar, Gondar, Ethiopia
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7
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Gray S, Ottensmeier CH. Advancing Understanding of Non-Small Cell Lung Cancer with Multiplexed Antibody-Based Spatial Imaging Technologies. Cancers (Basel) 2023; 15:4797. [PMID: 37835491 PMCID: PMC10571797 DOI: 10.3390/cancers15194797] [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: 08/21/2023] [Revised: 09/22/2023] [Accepted: 09/27/2023] [Indexed: 10/15/2023] Open
Abstract
Non-small cell lung cancer (NSCLC) remains a cause of significant morbidity and mortality, despite significant advances made in its treatment using immune checkpoint inhibitors (ICIs) over the last decade; while a minority experience prolonged responses with ICIs, benefit is limited for most patients. The development of multiplexed antibody-based (MAB) spatial tissue imaging technologies has revolutionised analysis of the tumour microenvironment (TME), enabling identification of a wide range of cell types and subtypes, and analysis of the spatial relationships and interactions between them. Such study has the potential to translate into a greater understanding of treatment susceptibility and resistance, factors influencing prognosis and recurrence risk, and identification of novel therapeutic approaches and rational treatment combinations to improve patient outcomes in the clinic. Herein we review studies that have leveraged MAB technologies to deliver novel insights into the TME of NSCLC.
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Affiliation(s)
- Simon Gray
- Department of Molecular and Clinical Cancer Medicine, Faculty of Health and Life Sciences, University of Liverpool, Ashton St., Liverpool L69 3GB, UK
- Department of Medical Oncology, The Clatterbridge Cancer Centre NHS Foundation Trust, Pembroke Pl., Liverpool L7 8YA, UK
| | - Christian H. Ottensmeier
- Department of Molecular and Clinical Cancer Medicine, Faculty of Health and Life Sciences, University of Liverpool, Ashton St., Liverpool L69 3GB, UK
- Department of Medical Oncology, The Clatterbridge Cancer Centre NHS Foundation Trust, Pembroke Pl., Liverpool L7 8YA, UK
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8
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Birse N, Burns DT, Walker MJ, Quaglia M, Elliott CT. Food allergen analysis: A review of current gaps and the potential to fill them by matrix-assisted laser desorption/ionization. Compr Rev Food Sci Food Saf 2023; 22:3984-4003. [PMID: 37530543 DOI: 10.1111/1541-4337.13216] [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: 10/28/2022] [Revised: 07/01/2023] [Accepted: 07/10/2023] [Indexed: 08/03/2023]
Abstract
Food allergy remains a public health, business, and regulatory challenge. Risk analysis (RA) and risk management (RM) of food allergens are of great importance and analysis for food allergens is necessary for both. The current workhorse techniques for allergen analysis (enzyme linked immunosorbent assay [ELISA] and real-time polymerase chain reaction) exhibit recognized challenges including variable and antibody specific responses and detection of species DNA rather than allergen protein, respectively. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables protein identification, with potential for multiplex analysis and traceability to the System of International units (SI), aiding global measurement standardization. In this review, recent literature has been systematically reviewed to assess progress in LC-MS/MS and define the potential and benefits of matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-ToF-MS) technology for allergen analysis. MALDI-ToF-MS of initially intact protein is already applied to verify in silico-derived peptide sequences for LC-MS/MS analysis. We describe the origins of MALDI and its future perspectives, including affinity bead-assisted assays coupled to MALDI. Based on the proliferation of reliable and reproducible MALDI-based clinical applications, the technique should emulate the detection capability (sensitivity) of established allergen detection techniques, whilst reducing technical support and having equivalent multiplexing potential to competing techniques, for example, LC-MS/MS and ELISA. Although unlikely to offer inherent SI traceability, MALDI-based allergen analysis will complement existing MS approaches for allergens. Affinity bead-MALDI appears capable of higher throughput at lower cost per sample than almost any existing technique, enabling repeated sub-sampling as a way to reduce representative sampling issues.
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Affiliation(s)
- Nicholas Birse
- Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Duncan Thorburn Burns
- Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK
| | - Michael J Walker
- Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK
| | | | - Christopher T Elliott
- Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, Belfast, Northern Ireland, UK
- School of Food Science and Technology, Faculty of Science and Technology, Thammasat University (Rangsit Campus), Khlong Luang, Pathum Thani, Thailand
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9
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Chen L, Ghiasvand A, Paull B. Applications of thread-based microfluidics: Approaches and options for detection. Trends Analyt Chem 2023. [DOI: 10.1016/j.trac.2023.117001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/02/2023]
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10
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Kartsova LA, Bessonova EA, Deev VA, Kolobova EA. Current Role of Modern Chromatography with Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy in the Investigation of Biomarkers of Endometriosis. Crit Rev Anal Chem 2023; 54:2110-2133. [PMID: 36625278 DOI: 10.1080/10408347.2022.2156770] [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] [Indexed: 01/11/2023]
Abstract
Endometriosis has a wide range of clinical manifestations, and the disease course is unpredictable, making the diagnosis a challenging task. Despite significant advances in the pathophysiology of endometriosis and various proposed theories, the exact etiology is not fully understood and is still unknown. The most commonly used biomarker of endometriosis is CA-125, however, it is nonspecific and is applied for cancers diagnosis. Therefore, the development of reliable noninvasive diagnostic tests for the early diagnosis of endometriosis remains one of the top priorities. Omics technologies are very promising approaches for constructing diagnostic models and biomarker discovery. Their use can greatly facilitate the study of such a complex disease as endometriosis. Nowadays, powerful analytical platforms commonly used in omics, such as gas and liquid chromatography with mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy, have proven to be a promising tools for biomarker discovery. The aim of this review is to summarize the various features of the analytical approaches, practical challenges and features of gas and liquid chromatography with MS and NMR spectroscopy (including sample processing protocols, technological advancements, and methodology) used for profiling of metabolites, lipids, peptides and proteins in physiological fluids and tissues from patients with endometriosis. In addition, this report devotes special attention to the issue of how comprehensive analyses of these profiles can effectively contribute to the study of endometriosis. The search query included reports published between 2012 and 2022 years in PubMed, Web-of-Science, SCOPUS, Science Direct.
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Affiliation(s)
| | | | | | - Ekaterina Alekseevna Kolobova
- Institute of Chemistry, St. Petersburg State University, St. Petersburg, Russia
- The Federal State Institute of Public Health 'The Nikiforov Russian Center of Emergency and Radiation Medicine', The Ministry of Russian Federation for Civil Defence, Emergencies and Elimination of Consequences of Natural Disasters, St. Petersburg, Russia
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11
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Hassan T, Firdous P, Nissar K, Ahmad MB, Imtiyaz Z. Role of proteomics in surgical oncology. Proteomics 2023. [DOI: 10.1016/b978-0-323-95072-5.00012-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/01/2023]
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12
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Pu K, Qiu J, Li J, Huang W, Lai X, Liu C, Lin Y, Ng KM. MALDI-TOF MS Protein Profiling Combined with Multivariate Analysis for Identification and Quantitation of Beef Adulteration. FOOD ANAL METHOD 2022. [DOI: 10.1007/s12161-022-02403-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
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13
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Wang HJ, Xie YB, Zhang PJ, Jiang T. Evaluation of the diagnostic value of serum-based proteomics for colorectal cancer. World J Gastrointest Oncol 2022; 14:1562-1573. [PMID: 36160749 PMCID: PMC9412932 DOI: 10.4251/wjgo.v14.i8.1562] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/08/2022] [Revised: 04/13/2022] [Accepted: 07/18/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a highly malignant cancer with a high incidence and mortality in China. It is urgent to find a diagnostic marker with higher sensitivity and specificity than the traditional approaches for CRC diagnosis.
AIM To provide new ideas for the diagnosis of CRC based on serum proteomics.
METHODS Specimens from 83 healthy people, 62 colon polyp (CRP) patients, and 101 CRC patients were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The diagnostic value of the profiles of differentially expressed proteins was then analyzed.
RESULTS Compared with the healthy control group, CRC patients had elevated expression of 5 proteins and reduced expression of 14 proteins. The area under the curve (AUC) for a differentially expressed protein with a mass-to-charge ratio of 2022.34 was the largest; the AUC was 0.843, which was higher than the AUC of 0.717 observed with carcinoembryonic antigen (CEA), and the sensitivity and specificity of this identified marker were 75.3% and 79.5%, respectively. After cross-validation, the accuracy of diagnosis using levels of this differentially expressed protein was 82.37%. Compared with the CRP group, the expression of 3 proteins in the serum of CRC patients was elevated and 11 proteins were expressed at reduced levels. Proteins possessing mass-to-charge ratio values of 2899.38 and 877.3 were selected to establish a classification tree model. The results showed that the accuracy of CRC diagnosis was 89.5%, the accuracy of CRP diagnosis was 81.6%, and the overall accuracy of this approach was 86.3%. The overall sensitivity and specificity of diagnosis using the proteomics approach were 81.8% and 66.75%, respectively. The sensitivities and specificities of diagnoses based on CEA and carbohydrate antigen 19-9 expression were 55.6% and 91.3% and 65.4% and 65.2%, respectively.
CONCLUSION We demonstrated that serum proteomics may be helpful for the detection of CRC, and it may assist clinical practice for CRC diagnosis.
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Affiliation(s)
- Hui-Juan Wang
- Department of Respiratory and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing 100020, China
| | - Yi-Bin Xie
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Peng-Jun Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Interventional Therapy Department, Peking University Cancer Hospital and Institute, Beijing 100142, China
| | - Tao Jiang
- Medical Innovation Research Division of Chinese PLA General Hospital, Beijing 100853, China
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14
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Circulating and non-circulating proteins and nucleic acids as biomarkers and therapeutic molecules in ovarian cancer. Genes Dis 2022. [DOI: 10.1016/j.gendis.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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15
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Zambonin C, Aresta A. MALDI-TOF/MS Analysis of Non-Invasive Human Urine and Saliva Samples for the Identification of New Cancer Biomarkers. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27061925. [PMID: 35335287 PMCID: PMC8951187 DOI: 10.3390/molecules27061925] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 03/06/2022] [Accepted: 03/14/2022] [Indexed: 01/22/2023]
Abstract
Cancer represents a group of heterogeneous diseases that are a leading global cause of death. Even though mortality has decreased in the past thirty years for different reasons, most patients are still diagnosed at the advanced stage, with limited therapeutic choices and poor outcomes. Moreover, the majority of cancers are detected using invasive painful methods, such as endoscopic biopsy, making the development of non-invasive or minimally invasive methods for the discovery and fast detection of specific biomarkers a crucial need. Among body fluids, a valuable non-invasive alternative to tissue biopsy, the most accessible and least invasive are undoubtedly urine and saliva. They are easily retrievable complex fluids containing a large variety of endogenous compounds that may provide information on the physiological condition of the body. The combined analysis of these fluids with matrix-assisted laser desorption ionization–time-of-flight mass spectrometry (MALDI-TOF/MS), a reliable and easy-to-use instrumentation that provides information with relatively simple sample pretreatments, could represent the ideal option to rapidly achieve fast early stage diagnosis of tumors and their real-time monitoring. On this basis, the present review summarizes the recently reported applications relevant to the MALDI analysis of human urine and saliva samples.
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16
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Gill EL, Patel K, Rakheja D. Oncometabolites and their role in cancer. Cancer Biomark 2022. [DOI: 10.1016/b978-0-12-824302-2.00003-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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17
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Lazari LC, Rosa-Fernandes L, Palmisano G. Identification of Circulating Biomarkers of COVID-19 Using MALDI-TOF Mass Spectrometry. Methods Mol Biol 2022; 2511:175-182. [PMID: 35838960 DOI: 10.1007/978-1-0716-2395-4_13] [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] [Indexed: 06/15/2023]
Abstract
Matrix-assisted laser desorption/ionization source coupled with time-of-flight mass analyzer mass spectrometry (MALDI-TOF MS) is being widely used to obtain proteomic profiles for clinical purposes, as a fast, low-cost, robust, and efficient technique. Here we describe a method for biofluid analysis using MALDI-TOF MS for rapid acquisition of proteomic signatures of COVID-19 infected patients. By using solid-phase extraction, the method allows the analysis of biofluids in less than 15 min.
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Affiliation(s)
- Lucas C Lazari
- GlycoProteomics Laboratory, Department of Parasitology, ICB, University of São Paulo, São Paulo, Brazil
| | - Livia Rosa-Fernandes
- GlycoProteomics Laboratory, Department of Parasitology, ICB, University of São Paulo, São Paulo, Brazil
| | - Giuseppe Palmisano
- GlycoProteomics Laboratory, Department of Parasitology, ICB, University of São Paulo, São Paulo, Brazil.
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18
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Zubair F. MALDI mass Spectrometry based proteomics for drug discovery & development. DRUG DISCOVERY TODAY. TECHNOLOGIES 2021; 40:29-35. [PMID: 34916018 DOI: 10.1016/j.ddtec.2021.09.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/08/2021] [Accepted: 09/08/2021] [Indexed: 12/19/2022]
Abstract
Matrix-assisted laser desorption/ ionization (MALDI) is a soft ionization technique for introducing wide range of analytes into a mass spectrometer (MS). MALDI MS is a powerful tool in drug discovery research and development, providing a high-throughput molecular analysis technique in both preclinical and clinical systems. In particular, MALDI MS is invaluable in the study of peptides and proteins that drive all biological functions. This technology is label-free, provides high specificity in molecular identification, and is high-throughput. MALDI MS has been used in biomarker discovery and quantitation in virtually all tissues, serum, plasma, CSF, and urine for diagnostics, patient stratification, and monitoring drug efficacy. Other applications include characterization of biological drugs, spatial mapping of biomarkers and drugs in tissues, drug screening, and toxicological assessment.
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19
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Bertok T, Pinkova Gajdosova V, Bertokova A, Svecova N, Kasak P, Tkac J. Breast cancer glycan biomarkers: their link to tumour cell metabolism and their perspectives in clinical practice. Expert Rev Proteomics 2021; 18:881-910. [PMID: 34711108 DOI: 10.1080/14789450.2021.1996231] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Breast cancer (BCa) is the most common cancer type diagnosed in women and 5th most common cause of deaths among all cancer deaths despite the fact that screening program is at place. This is why novel diagnostics approaches are needed in order to decrease number of BCa cases and disease mortality. AREAS COVERED In this review paper, we aim to cover some basic aspects regarding cellular metabolism and signalling in BCa behind altered glycosylation. We also discuss novel exciting discoveries regarding glycan-based analysis, which can provide useful information for better understanding of the disease. The final part deals with clinical usefulness of glycan-based biomarkers and the clinical performance of such biomarkers is compared to already approved BCa biomarkers and diagnostic tools based on imaging. EXPERT OPINION Recent discoveries suggest that glycan-based biomarkers offer high accuracy for possible BCa diagnostics in blood, but also for better monitoring and management of BCa patients. The review article was written using Web of Science search engine to include articles published between 2019 and 2021.
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Affiliation(s)
- Tomas Bertok
- Glycanostics Ltd., Bratislava, Slovak Republic.,Department of Glycobiotechnology, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic
| | - Veronika Pinkova Gajdosova
- Department of Glycobiotechnology, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic
| | | | - Natalia Svecova
- Department of Glycobiotechnology, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic
| | - Peter Kasak
- Center for Advanced Materials, Qatar University, Doha, Qatar
| | - Jan Tkac
- Glycanostics Ltd., Bratislava, Slovak Republic.,Department of Glycobiotechnology, Institute of Chemistry, Slovak Academy of Sciences, Bratislava, Slovak Republic
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20
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Jiang X, Chen X, Chen Z, Yu J, Lou H, Wu J. High-Throughput Salivary Metabolite Profiling on an Ultralow Noise Tip-Enhanced Laser Desorption Ionization Mass Spectrometry Platform for Noninvasive Diagnosis of Early Lung Cancer. J Proteome Res 2021; 20:4346-4356. [PMID: 34342461 DOI: 10.1021/acs.jproteome.1c00310] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Lung cancer (LC) is a widespread cancer that is the cause of the highest mortality rate accounting for 25% of all cancer deaths. To date, most LC patients are diagnosed at the advanced stage owing to the lack of obvious symptoms in the early stage and the limitations of current clinical diagnostic techniques. Therefore, developing a high throughput technique for early screening is of great importance. In this work, we established an effective and rapid salivary metabolic analysis platform for early LC diagnosis and combined metabolomics and transcriptomics to reveal the metabolic fluctuations correlated to LC. Saliva samples were collected from a total of 150 volunteers including 89 patients with early LC, 11 patients with advanced LC, and 50 healthy controls. The metabolic profiling of noninvasive samples was investigated on an ultralow noise TELDI-MS platform. In addition, data normalization methods were screened and assessed to overcome the MS signal variation caused by individual difference for biomarker mining. For untargeted metabolic profiling of saliva samples, around 264 peaks could be reliably detected in each sample. After multivariate analysis, 23 metabolites were sorted out and verified to be related to the dysfunction of the amino acid and nucleotide metabolism in early LC. Notably, transcriptomic data from online TCGA repository were utilized to support findings from the salivary metabolomics experiment, including the disorder of amino acid biosynthesis and amino acid metabolism. Based on the verified differential metabolites, early LC patients could be clearly distinguished from healthy controls with a sensitivity of 97.2% and a specificity of 92%. The ultralow noise TELDI-MS platform displayed satisfactory ability to explore salivary metabolite information and discover potential biomarkers that may help develop a noninvasive screening tool for early LC.
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Affiliation(s)
- Xinrong Jiang
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China
| | - Xiaoming Chen
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China.,Well-Healthcare Technologies Co., Hangzhou 310051, China
| | - Zhao Chen
- Department of Thoracic Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Jiekai Yu
- Institute of Cancer Research, The Second Affiliated Hospital of Zhejiang University, Hangzhou 310009, China
| | - Haizhou Lou
- Department of Medical Oncology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China
| | - Jianmin Wu
- Institution of Analytical Chemistry, Department of Chemistry, Zhejiang University, Hangzhou 310058, China
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21
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Yu Z, Zhao C, Hu S, Zhang H, Li W, Zhang R, Luo Q, Yang H. MALDI-MS-based biomarker analysis of extracellular vesicles from human lung carcinoma cells. RSC Adv 2021; 11:25375-25380. [PMID: 35478925 PMCID: PMC9037017 DOI: 10.1039/d1ra04305f] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 07/12/2021] [Indexed: 12/19/2022] Open
Abstract
Extracellular vesicles (EVs) are actively secreted by mammalian cells. They are increasingly recognized as promising circulating biomarkers of disease progression. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is currently one of the most powerful techniques for the rapid analysis of biological samples, especially for discovering biomarkers for disease diagnosis and prognosis. It is unclear what cell culture medium components and EV isolation methods are suitable for MALDI-TOF MS analysis. Using a human lung carcinoma cell line (A549), we investigated and optimized the critical experimental conditions for EVs' protein profiling by combining differential ultracentrifugation and MALDI-TOF MS. The results demonstrated that medium components and ultracentrifugation procedures to extract EVs played important roles in MS detection. Compared with EV-depleted serum and normal serum medium, conditioned medium with 2% fetal bovine serum in this study maintained cell proliferation and displayed significant protein profiling of EVs. RPS27A (ribosomal protein), which plays an essential role in mRNA translation and ribosome assembly for the differentiation of cancer cells, was detected from the EVs of lung cancer cells associated with cancer cell migration and invasion. We also found the known tumor diagnosis marker, which is S100A10_S100 calcium-binding protein A10. Therefore, MALDI-TOF MS-based EV analysis with optimized experimental protocols can contribute to future development of rapid screening techniques of protein biomarkers associated with early cancer diagnosis.
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Affiliation(s)
- Zitong Yu
- Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
| | - Chao Zhao
- Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
| | - Shi Hu
- Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
| | - Huitao Zhang
- Research Center for Medical Artificial Intelligence, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
| | - Wenbo Li
- Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
| | - Renjie Zhang
- Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
| | - Qian Luo
- Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
| | - Hui Yang
- Bionic Sensing and Intelligence Center, Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China .,CAS Key Laboratory of Health Informatics, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences Shenzhen 518055 China
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22
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Detection of Hepatocellular Carcinoma in a High-Risk Population by a Mass Spectrometry-Based Test. Cancers (Basel) 2021; 13:cancers13133109. [PMID: 34206321 PMCID: PMC8268628 DOI: 10.3390/cancers13133109] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2021] [Revised: 06/12/2021] [Accepted: 06/14/2021] [Indexed: 02/07/2023] Open
Abstract
Simple Summary Liver cancer is one of the most common causes of cancer worldwide, but unfortunately, current technology has a limited ability to detect it early in high-risk patients. This study investigates a machine learning algorithm based on protein levels in the blood that can be used to help with diagnosis. The test shows promising results, especially in patients with smaller tumors and compared to current blood detection tests. This research suggests an important role in the future for machine learning algorithm-based blood detection tests. Abstract Hepatocellular carcinoma (HCC) is one of the fastest growing causes of cancer-related death. Guidelines recommend obtaining a screening ultrasound with or without alpha-fetoprotein (AFP) every 6 months in at-risk adults. AFP as a screening biomarker is plagued by low sensitivity/specificity, prompting interest in discovering alternatives. Mass spectrometry-based techniques are promising in their ability to identify potential biomarkers. This study aimed to use machine learning utilizing spectral data and AFP to create a model for early detection. Serum samples were collected from three separate cohorts, and data were compiled to make Development, Internal Validation, and Independent Validation sets. AFP levels were measured, and Deep MALDI® analysis was used to generate mass spectra. Spectral data were input into the VeriStrat® classification algorithm. Machine learning techniques then classified each sample as “Cancer” or “No Cancer”. Sensitivity and specificity of the test were >80% to detect HCC. High specificity of the test was independent of cause and severity of underlying disease. When compared to AFP, there was improved cancer detection for all tumor sizes, especially small lesions. Overall, a machine learning algorithm incorporating mass spectral data and AFP values from serum samples offers a novel approach to diagnose HCC. Given the small sample size of the Independent Validation set, a further independent, prospective study is warranted.
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23
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Liu S, Yu Y, Liu Y, Lin J, Fu Y, Cheng L, Liu X. Revealing the changes of IgG subclass-specific N-glycosylation in colorectal cancer progression by high-throughput assay. Proteomics Clin Appl 2021; 15:e2000022. [PMID: 33599092 DOI: 10.1002/prca.202000022] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 10/26/2020] [Accepted: 12/17/2020] [Indexed: 12/16/2022]
Abstract
PURPOSE The changes of glycosylation of different IgG subclass in colorectal cancer (CRC) were rarely investigated. The authors aimed to use a simple and high-throughput analytical method to explore the changes of subclass-specific IgG glycosylation in CRC, and to find the specific glyco-biomarkers for early detection of this disease. EXPERIMENTAL DESIGN Serum samples from 71 cancer patients and 22 benign patients with 50 age- and sex-matched healthy controls were collected from two independent cohorts. Subclass-specific IgG glycosylation was profiled by MALDI-MS followed by the structural identification through MALDI-MS/MS. The exported MS data was automatically and rapidly processed by the self-developed MATLAB code. RESULTS Statistical analysis suggested the significantly decreased galactosylation and remarkably increased agalactosylation of IgG1 or IgG2 in the malignant transformation of CRC, which enables the differentiation between cancer patients and healthy controls. The changes of glycan features were elucidated by the exploration of individual glycopeptides, showing the biantennary fucosylated glycan without galactose (H3N4F1) or with two galactose (H5N4F1) of IgG1 and IgG2 could distinguish cancer group from both benign and control groups. CONCLUSIONS AND CLINICAL RELEVANCE Through the simple and high-throughput procedures, this study revealed the important role of IgG glycopeptides in the premature pathology of CRC.
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Affiliation(s)
- Si 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, Wuhan, China
| | - Yuting Yu
- Wuhan Institute of Biological products, Wuhan, 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, Wuhan, 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, Wuhan, China
| | - Yang Fu
- 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, Wuhan, China
| | - Liming Cheng
- Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 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, Wuhan, China
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24
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Jiang X, Chen X, Wang T, Li Y, Pan A, Wu J. Perfluorinated polymer modified vertical silicon nanowires as ultra low noise laser desorption ionization substrate for salivary metabolites profiling. Talanta 2021; 225:122022. [DOI: 10.1016/j.talanta.2020.122022] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 12/07/2020] [Accepted: 12/13/2020] [Indexed: 12/12/2022]
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25
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Analytical Platforms for the Determination of Phospholipid Turnover in Breast Cancer Tissue: Role of Phospholipase Activity in Breast Cancer Development. Metabolites 2021; 11:metabo11010032. [PMID: 33406793 PMCID: PMC7824782 DOI: 10.3390/metabo11010032] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 12/26/2020] [Accepted: 12/31/2020] [Indexed: 12/31/2022] Open
Abstract
Altered lipid metabolism has been associated with the progression of various cancers, and aberrant expression of enzymes involved in the lipid metabolism has been detected in different stages of cancer. Breast cancer (BC) is one of the cancer types known to be associated with alterations in the lipid metabolism and overexpression of enzymes involved in this metabolism. It has been demonstrated that inhibition of the activity of certain enzymes, such as that of phospholipase A2 in BC cell lines sensitizes these cells and decreases the IC50 values for forthcoming therapy with traditional drugs, such as doxorubicin and tamoxifen. Moreover, other phospholipases, such as phospholipase C and D, are involved in intracellular signal transduction, which emphasizes their importance in cancer development. Finally, BC is assumed to be dependent on the diet and the composition of lipids in nutrients. Despite their importance, analytical approaches that can associate the activity of phospholipases with changes in the lipid composition and distribution in cancer tissues are not yet standardized. In this review, an overview of various analytical platforms that are applied on the study of lipids and phospholipase activity in BC tissues will be given, as well as their association with cancer diagnosis and tumor progression. The methods that are applied to tissues obtained from the BC patients will be emphasized and critically evaluated, regarding their applicability in oncology.
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26
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Hauser JR, Bergström ET, Kulak AN, Warriner SL, Thomas-Oates J, Bon RS. Pyrene Tags for the Detection of Carbohydrates by Label-Assisted Laser Desorption/Ionisation Mass Spectrometry*. Chembiochem 2021; 22:1430-1439. [PMID: 33296552 DOI: 10.1002/cbic.202000721] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 12/08/2020] [Indexed: 12/15/2022]
Abstract
Matrix-assisted laser desorption/ionisation mass spectrometry (MALDI-MS) is widely used for the analysis of biomolecules. Label-assisted laser desorption/ionisation mass spectrometry (LALDI-MS) is a matrix-free variant of MALDI-MS, in which only analytes covalently attached to a laser desorption/ionisation (LDI) enhancer are detected. LALDI-MS has shown promise in overcoming the limitations of MALDI-MS in terms of sample preparation and MS analysis. In this work, we have developed a series of pyrene-based LDI reagents (LALDI tags) that can be used for labelling and LALDI-MS analysis of reducing carbohydrates from complex (biological) samples without the need for additional chemical derivatisation or purification. We have systematically explored the suitability of four pyrene-based LDI enhancers and three aldehyde-reactive handles, optimised sample preparation, and demonstrated the use of LALDI tags for the detection of lactose. We have also exemplified the potential of LALDI tags for labelling carbohydrates in biological samples by direct detection of lactose in cow's milk. These results demonstrate that LALDI-MS is a promising technique for the analysis of reducing carbohydrates in biological samples, and pave the way for the development of LALDI-MS for glycomics and diagnostics.
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Affiliation(s)
- Jacob R Hauser
- School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.,Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK
| | - Edmund T Bergström
- Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.,Centre of Excellence in Mass Spectrometry, University of York, Heslington, York, YO10 5DD, UK
| | - Alexander N Kulak
- School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK
| | - Stuart L Warriner
- School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.,Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK
| | - Jane Thomas-Oates
- Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK.,Centre of Excellence in Mass Spectrometry, University of York, Heslington, York, YO10 5DD, UK
| | - Robin S Bon
- Astbury Centre for Structural Molecular Biology, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK.,Discovery and Translational Science Department, Leeds Institute of Cardiovascular and Metabolic Medicine, LIGHT Laboratories, University of Leeds, Leeds, LS2 9JT, UK
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27
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Arendowski A, Ossolinski K, Niziol J, Ruman T. Screening of Urinary Renal Cancer Metabolic Biomarkers with Gold Nanoparticles-assisted Laser Desorption/Ionization Mass Spectrometry. ANAL SCI 2020; 36:1521-1525. [PMID: 32830161 DOI: 10.2116/analsci.20p226] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2020] [Accepted: 08/13/2020] [Indexed: 08/09/2023]
Abstract
Renal cell carcinoma is a very aggressive and often fatal disease for which there are no specific biomarkers found to date. The purpose of this work was to find features that differentiate urine metabolic profiles of healthy people and cancer patients. Laser desorption/ionization mass spectrometry on gold nanostructures-based techniques were used for the metabolic analysis of urine of 50 patients with kidney cancer. Comparison with data from 50 healthy volunteers led to the discovery of several compounds that may be considered potential renal cell carcinoma (RCC) biomarkers. Statistical analysis of data allowed for the discovery of m/z values that had the greatest impact on group differentiation. A database search enabled the assignment of signals for the most promising 15 features among them: serine, heptanol, 3-methylene-indolenine, 2-methyl-3-hydroxy-5-formylpyridine-4-carboxylate, phosphodimethylethanolamine, 4-methoxyphenylacetic acid, N-acetylglutamine, 3,5-dihydroxyphenylvaleric acid, hydroxyhexanoylglycine, valyl-leucine, leucyl-histidine, oleamide, 9,12,13-trihydroxyoctadecenoic acid, stearidonyl carnitine and squalene. Differences of metabolite profiles of human urine could be identified by gold nanoparticle-enhanced target (AuNPET) LDI MS method and used for the detection of renal cancer.
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Affiliation(s)
- Adrian Arendowski
- Faculty of Chemistry, Rzeszów University of Technology, 6 Powstańców Warszawy Ave, 35-959, Rzeszów, Poland
| | - Krzysztof Ossolinski
- Department of Urology, John Paul II District Hospital, Grunwaldzka 4 St, 36-100, Kolbuszowa, Poland
| | - Joanna Niziol
- Faculty of Chemistry, Rzeszów University of Technology, 6 Powstańców Warszawy Ave, 35-959, Rzeszów, Poland
| | - Tomasz Ruman
- Faculty of Chemistry, Rzeszów University of Technology, 6 Powstańców Warszawy Ave, 35-959, Rzeszów, Poland
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Jayathirtha M, Dupree EJ, Manzoor Z, Larose B, Sechrist Z, Neagu AN, Petre BA, Darie CC. Mass Spectrometric (MS) Analysis of Proteins and Peptides. Curr Protein Pept Sci 2020; 22:92-120. [PMID: 32713333 DOI: 10.2174/1389203721666200726223336] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2020] [Revised: 05/12/2020] [Accepted: 05/28/2020] [Indexed: 01/09/2023]
Abstract
The human genome is sequenced and comprised of ~30,000 genes, making humans just a little bit more complicated than worms or flies. However, complexity of humans is given by proteins that these genes code for because one gene can produce many proteins mostly through alternative splicing and tissue-dependent expression of particular proteins. In addition, post-translational modifications (PTMs) in proteins greatly increase the number of gene products or protein isoforms. Furthermore, stable and transient interactions between proteins, protein isoforms/proteoforms and PTM-ed proteins (protein-protein interactions, PPI) add yet another level of complexity in humans and other organisms. In the past, all of these proteins were analyzed one at the time. Currently, they are analyzed by a less tedious method: mass spectrometry (MS) for two reasons: 1) because of the complexity of proteins, protein PTMs and PPIs and 2) because MS is the only method that can keep up with such a complex array of features. Here, we discuss the applications of mass spectrometry in protein analysis.
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Affiliation(s)
- Madhuri Jayathirtha
- Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY, United States
| | - Emmalyn J Dupree
- Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY, United States
| | - Zaen Manzoor
- Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY, United States
| | - Brianna Larose
- Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY, United States
| | - Zach Sechrist
- Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY, United States
| | - Anca-Narcisa Neagu
- Laboratory of Animal Histology, Faculty of Biology, "Alexandru Ioan Cuza" University of Iasi, Iasi, Romania
| | - Brindusa Alina Petre
- Laboratory of Biochemistry, Department of Chemistry, Al. I. Cuza University of Iasi, Iasi, Romania, Center for Fundamental Research and Experimental Development in Translation Medicine - TRANSCEND, Regional Institute of Oncology, Iasi, Romania
| | - Costel C Darie
- Biochemistry & Proteomics Group, Department of Chemistry and Biomolecular Science, Clarkson University, 8 Clarkson Avenue, Potsdam, NY, United States
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Berghmans E, Jacobs J, Deben C, Hermans C, Broeckx G, Smits E, Maes E, Raskin J, Pauwels P, Baggerman G. Mass Spectrometry Imaging Reveals Neutrophil Defensins as Additional Biomarkers for Anti-PD-(L)1 Immunotherapy Response in NSCLC Patients. Cancers (Basel) 2020; 12:E863. [PMID: 32252405 PMCID: PMC7225984 DOI: 10.3390/cancers12040863] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Revised: 03/30/2020] [Accepted: 04/01/2020] [Indexed: 12/17/2022] Open
Abstract
(1) Background: Therapeutic blocking of the interaction between programmed death-1 (PD-1) with its ligand PD-L1, an immune checkpoint, is a promising approach to restore the antitumor immune response. Improved clinical outcomes have been shown in different human cancers, including non-small cell lung cancer (NSCLC). Unfortunately, still a high number of NSCLC patients are treated with immunotherapy without obtaining any clinical benefit, due to the limitations of PD-L1 protein expression as the currently sole predictive biomarker for clinical use; (2) Methods: In this study, we applied mass spectrometry imaging (MSI) to discover new protein biomarkers, and to assess the possible correlation between candidate biomarkers and a positive immunotherapy response by matrix-assisted laser desorption/ionization (MALDI) MSI in 25 formalin-fixed paraffin-embedded (FFPE) pretreatment tumor biopsies (Biobank@UZA); (3) Results: Using MALDI MSI, we revealed that the addition of neutrophil defensin 1, 2 and 3 as pretreatment biomarkers may more accurately predict the outcome of immunotherapy treatment in NSCLC. These results were verified and confirmed with immunohistochemical analyses. In addition, we provide in-vitro evidence of the immune stimulatory effect of neutrophil defensins towards cancer cells; and (4) Conclusions: With proteomic approaches, we have discovered neutrophil defensins as additional prospective biomarkers for an anti-PD-(L)1 immunotherapy response. Thereby, we also demonstrated that the neutrophil defensins contribute in the activation of the immune response towards cancer cells, which could provide a new lead towards an anticancer therapy.
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Affiliation(s)
- Eline Berghmans
- Centre for Proteomics, University of Antwerp, 2020 Antwerpen, Belgium;
- Health Unit, VITO, 2400 Mol, Belgium
| | - Julie Jacobs
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Christophe Deben
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Christophe Hermans
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Glenn Broeckx
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Evelien Smits
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Evelyne Maes
- Food & Bio-Based Products, AgResearch Ltd., Lincoln 7674, New Zealand;
| | - Jo Raskin
- Thoracic Oncology Department, Antwerp University Hospital, 2650 Edegem, Belgium;
| | - Patrick Pauwels
- Center for Oncological Research, University of Antwerp, 2610 Wilrijk, Belgium; (J.J.); (C.D.); (C.H.); (G.B.); (E.S.); (P.P.)
- Pathology Department, Antwerp University Hospital, 2650 Edegem, Belgium
| | - Geert Baggerman
- Centre for Proteomics, University of Antwerp, 2020 Antwerpen, Belgium;
- Health Unit, VITO, 2400 Mol, Belgium
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Cantor DI, Cheruku HR, Westacott J, Shin JS, Mohamedali A, Ahn SB. Proteomic investigations into resistance in colorectal cancer. Expert Rev Proteomics 2020; 17:49-65. [PMID: 31914823 DOI: 10.1080/14789450.2020.1713103] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Introduction: Despite advances in screening and treatment options, colorectal cancer (CRC) remains one of the most prevalent and lethal cancer subtypes. Resistance to cytotoxic or targeted therapy has remained a constant challenge to the treatment and long-term management of patients, attracting intense worldwide investigation since the 1950s. Through extensive investigations into the proteomic mechanisms and functions that convey resistance to therapy/s, researchers have become able to implicate alterations in several signaling pathways that provide and sustain resistance to treatment.Areas covered: In this review, we summarize how protein alterations are associated with resistance to therapy, with particular emphasis on CRC. An overview of the mechanisms of therapeutic resistance is described, highlighting recent studies which endeavor to elucidate the proteomic changes that are associated with the acquisition and promulgation of therapeutic resistance.Expert opinion: While cancers such as CRC have been intensively studied for decades, unresponsiveness and the resistance to therapy remain critical obstacles in the treatment of patients. Due to the inherent biological and clinical heterogeneity of individual CRCs, proteomic methods stand to become powerful tools to provide biological insights that may guide therapeutic strategies with the ultimate goal of refining emergent immunotherapeutic treatments.
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Affiliation(s)
- David I Cantor
- Australian Proteome Analysis Facility, Macquarie University, Sydney, Australia
| | | | - Jack Westacott
- Faculty of Science and Engineering, Macquarie University, Sydney, Australia
| | - Joo-Shik Shin
- Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital and Faculty of Medicine, University of Sydney, Sydney, Australia
| | - Abidali Mohamedali
- Faculty of Science and Engineering, Macquarie University, Sydney, Australia
| | - Seong Boem Ahn
- Faculty of Health and Medical Sciences, Macquarie University, Sydney, Australia
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Galey MM, Young AN, Petukhova VZ, Wang M, Wang J, Salvi A, Russo A, Burdette JE, Sanchez LM. Detection of Ovarian Cancer Using Samples Sourced from the Vaginal Microenvironment. J Proteome Res 2020; 19:503-510. [PMID: 31738564 DOI: 10.1021/acs.jproteome.9b00694] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Mass spectrometry (MS) offers high levels of specificity and sensitivity in clinical applications, and we have previously been able to demonstrate that matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS is capable of distinguishing two-component cell mixtures at low limits of detection. Ovarian cancer is notoriously difficult to detect due to the lack of diagnostic techniques available to the medical community. By sampling a local microenvironment, such as the vaginal canal and cervix, a MS based method is presented for monitoring disease progression from proximal samples to the diseased tissue. A murine xenograft model of high grade serous ovarian carcinoma (HGSOC) was used for this study, and vaginal lavages were obtained from mice on a weekly basis throughout disease progression and subjected to our MALDI-TOF MS workflow followed by statistical analyses. Proteins in the 4-20 kDa region of the mass spectrum yielded a fingerprint that we could consistently measure over time that correlated with disease progression. These fingerprints were found to be largely stable across all mice, with the protein fingerprint converging toward the end point of the study. MALDI-TOF MS serves as a unique analytical technique for measuring a sampled vaginal microenvironment in a specific and sensitive manner for the detection of HGSOC in a murine model.
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Affiliation(s)
- Melissa M Galey
- Department of Pharmaceutical Sciences , University of Illinois at Chicago , 833 S Wood Street , Chicago , Illinois 60612 , United States
| | - Alexandria N Young
- Department of Pharmaceutical Sciences , University of Illinois at Chicago , 833 S Wood Street , Chicago , Illinois 60612 , United States
| | - Valentina Z Petukhova
- Department of Pharmaceutical Sciences , University of Illinois at Chicago , 833 S Wood Street , Chicago , Illinois 60612 , United States
| | - Mingxun Wang
- Ometa Laboratories , 3210 Merryfield Row , San Diego , California 92121 , United States
| | - Jian Wang
- Ometa Laboratories , 3210 Merryfield Row , San Diego , California 92121 , United States
| | - Amrita Salvi
- Department of Pharmaceutical Sciences , University of Illinois at Chicago , 833 S Wood Street , Chicago , Illinois 60612 , United States
| | - Angela Russo
- Department of Pharmaceutical Sciences , University of Illinois at Chicago , 833 S Wood Street , Chicago , Illinois 60612 , United States
| | - Joanna E Burdette
- Department of Pharmaceutical Sciences , University of Illinois at Chicago , 833 S Wood Street , Chicago , Illinois 60612 , United States
| | - Laura M Sanchez
- Department of Pharmaceutical Sciences , University of Illinois at Chicago , 833 S Wood Street , Chicago , Illinois 60612 , United States
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Horatz K, Ditte K, Prenveille T, Zhang K, Jehnichen D, Kiriy A, Voit B, Lissel F. Amorphous Conjugated Polymers as Efficient Dual‐Mode MALDI Matrices for Low‐Molecular‐Weight Analytes. Chempluschem 2019; 84:1338-1345. [DOI: 10.1002/cplu.201900203] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2019] [Revised: 06/14/2019] [Indexed: 11/11/2022]
Affiliation(s)
- Kilian Horatz
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
- Technische Universität Dresden Mommsenstraße 01062 Dresden Germany
| | - Kristina Ditte
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
- Technische Universität Dresden Mommsenstraße 01062 Dresden Germany
| | - Thomas Prenveille
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
- Technische Universität Dresden Mommsenstraße 01062 Dresden Germany
- Arkema S.A, Colombes, France
| | - Ke‐Nan Zhang
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
- Technische Universität Dresden Mommsenstraße 01062 Dresden Germany
| | - Dieter Jehnichen
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
| | - Anton Kiriy
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
| | - Brigitte Voit
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
- Technische Universität Dresden Mommsenstraße 01062 Dresden Germany
| | - Franziska Lissel
- Leibniz-Institut für Polymerforschung Dresden e.V. Hohe Straße 6 01069 Dresden Germany
- Technische Universität Dresden Mommsenstraße 01062 Dresden Germany
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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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Complementarity of Matrix- and Nanostructure-Assisted Laser Desorption/Ionization Approaches. NANOMATERIALS 2019; 9:nano9020260. [PMID: 30769830 PMCID: PMC6410089 DOI: 10.3390/nano9020260] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/30/2019] [Revised: 02/08/2019] [Accepted: 02/11/2019] [Indexed: 01/06/2023]
Abstract
In recent years, matrix-assisted laser desorption/ionization (MALDI) has become the main tool for the study of biological macromolecules, such as protein nano-machines, especially in the determination of their molecular masses, structure, and post-translational modifications. A key role in the classical process of desorption and ionization of the sample is played by a matrix, usually a low-molecular weight weak organic acid. Unfortunately, the interpretation of mass spectra in the mass range of below m/z 500 is difficult, and hence the analysis of low molecular weight compounds in a matrix-assisted system is an analytical challenge. Replacing the classical matrix with nanomaterials, e.g., silver nanoparticles, allows improvement of the selectivity and sensitivity of spectrometric measurement of biologically important small molecules. Nowadays, the nanostructure-assisted laser desorption/ionization (NALDI) approach complements the classic MALDI in the field of modern bioanalytics. In particular, the aim of this work is to review the recent advances in MALDI and NALDI approaches.
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An auxiliary matrix for routine analysis of small molecules and biological macromolecules using matrix-assisted laser desorption ionization mass spectrometry. Anal Bioanal Chem 2019; 411:1041-1052. [DOI: 10.1007/s00216-018-1532-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/21/2018] [Accepted: 11/30/2018] [Indexed: 12/26/2022]
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Lin M, Xu J, Liu X, Dai Z, Liu Z, Zhao X, Sun Y, Pu X. Metabolomics profiling of methamphetamine addicted human serum and three rat brain areas. RSC Adv 2019; 9:41107-41119. [PMID: 35540062 PMCID: PMC9076436 DOI: 10.1039/c9ra08096a] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2019] [Accepted: 11/29/2019] [Indexed: 12/23/2022] Open
Abstract
Methamphetamine (METH) has already been a serious problem all over the world. The identification of related biomarkers and pathways is helpful to evaluate the degree of METH addiction, develop appropriate treatment during abstinence, and explore the mechanism. Here, it is the first time to perform metabolomics profiling of METH addicted human serum and three regions of METH-induced conditioned place preference (CPP) rat brain by using UHPLC-MS/MS and matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), respectively. Untargeted metabolomics analysis demonstrated clear differences between METH abusers and the healthy control by finding 35 distinct expressed metabolites in serum, including 5 TCA intermediates, 17 amino acids and 13 other biomolecules, 15 of which were newly identified following METH exposure. By using MALDI-MSI, the relative quantification and distribution of 14 metabolites were investigated in the nucleus accumbens (NAc), dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) of CPP rat brain. Taken together, METH addiction could influence energy metabolism, amino acids metabolism, and phospholipids metabolism. A multi-parameter model consisting of these related metabolites can be established as a METH addiction biomarker in the future. The mapping of phospholipids provided new insights into the mechanism of METH addiction. Notably, the trend of metabolite changes in NAc and dHPC was almost the same, while it was opposite between dHPC and vHPC. It seems that NAc and dHPC were the two regions more susceptible to METH administration in the brain. And dHPC and vHPC play different roles in METH addiction proved by metabolites mapping. To explore the mechanism of METH addiction, the metabolomics profiling of METH addicted human serum and rat brain were performed using UHPLC-MS/MS and MALDI-MSI, respectively. 35 differentially expressed metabolites were identified in the serum.![]()
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Affiliation(s)
- Ming Lin
- National Key Research Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- China
- Department of Molecular and Cellular Pharmacology
| | - Jiamin Xu
- National Key Research Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- China
- Department of Molecular and Cellular Pharmacology
| | - Xi Liu
- National Key Research Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- China
- Department of Molecular and Cellular Pharmacology
| | - Zhenfeng Dai
- National Key Research Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- China
- Department of Molecular and Cellular Pharmacology
| | - Zhimin Liu
- National Institute on Drug Dependence
- Peking University
- Beijing
- China
| | - Xin Zhao
- National Key Research Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- China
- Department of Molecular and Cellular Pharmacology
| | - Yi Sun
- National Key Research Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- China
- Department of Molecular and Cellular Pharmacology
| | - Xiaoping Pu
- National Key Research Laboratory of Natural and Biomimetic Drugs
- Peking University
- Beijing
- China
- Department of Molecular and Cellular Pharmacology
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Swiatly A, Plewa S, Matysiak J, Kokot ZJ. Mass spectrometry-based proteomics techniques and their application in ovarian cancer research. J Ovarian Res 2018; 11:88. [PMID: 30270814 PMCID: PMC6166298 DOI: 10.1186/s13048-018-0460-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2018] [Accepted: 09/20/2018] [Indexed: 12/26/2022] Open
Abstract
Ovarian cancer has emerged as one of the leading cause of gynecological malignancies. So far, the measurement of CA125 and HE4 concentrations in blood and transvaginal ultrasound examination are essential ovarian cancer diagnostic methods. However, their sensitivity and specificity are still not sufficient to detect disease at the early stage. Moreover, applied treatment may appear to be ineffective due to drug-resistance. Because of a high mortality rate of ovarian cancer, there is a pressing need to develop innovative strategies leading to a full understanding of complicated molecular pathways related to cancerogenesis. Recent studies have shown the great potential of clinical proteomics in the characterization of many diseases, including ovarian cancer. Therefore, in this review, we summarized achievements of proteomics in ovarian cancer management. Since the development of mass spectrometry has caused a breakthrough in systems biology, we decided to focus on studies based on this technique. According to PubMed engine, in the years 2008-2010 the number of studies concerning OC proteomics was increasing, and since 2010 it has reached a plateau. Proteomics as a rapidly evolving branch of science may be essential in novel biomarkers discovery, therapy decisions, progression predication, monitoring of drug response or resistance. Despite the fact that proteomics has many to offer, we also discussed some limitations occur in ovarian cancer studies. Main difficulties concern both complexity and heterogeneity of ovarian cancer and drawbacks of the mass spectrometry strategies. This review summarizes challenges, capabilities, and promises of the mass spectrometry-based proteomics techniques in ovarian cancer management.
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Affiliation(s)
- Agata Swiatly
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 Street, 60-780 Poznań, Poland
| | - Szymon Plewa
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 Street, 60-780 Poznań, Poland
| | - Jan Matysiak
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 Street, 60-780 Poznań, Poland
| | - Zenon J. Kokot
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, Grunwaldzka 6 Street, 60-780 Poznań, Poland
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Greco V, Piras C, Pieroni L, Ronci M, Putignani L, Roncada P, Urbani A. Applications of MALDI-TOF mass spectrometry in clinical proteomics. Expert Rev Proteomics 2018; 15:683-696. [PMID: 30058389 DOI: 10.1080/14789450.2018.1505510] [Citation(s) in RCA: 49] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
INTRODUCTION The development of precision medicine requires advanced technologies to address the multifactorial disease stratification and to support personalized treatments. Among omics techniques, proteomics based on Mass Spectrometry (MS) is becoming increasingly relevant in clinical practice allowing a phenotypic characterization of the dynamic functional status of the organism. From this perspective, Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) MS is a suitable platform for providing a high-throughput support to clinics. Areas covered: This review aims to provide an updated overview of MALDI-TOF MS applications in clinical proteomics. The most relevant features of this analysis have been discussed, highlighting both pre-analytical and analytical factors that are crucial in proteomics studies. Particular emphasis is placed on biofluids proteomics for biomarkers discovery and on recent progresses in clinical microbiology, drug monitoring, and minimal residual disease (MRD). Expert commentary: Despite some analytical limitations, the latest technological advances together with the easiness of use, the low time and low cost consuming and the high throughput are making MALDI-TOF MS instruments very attractive for the clinical practice. These features offer a significant potential for the routine of the clinical laboratory and ultimately for personalized medicine.
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Affiliation(s)
- Viviana Greco
- a Institute of Biochemistry and Clinical Biochemistry , Università Cattolica del Sacro Cuore , Rome , Italy.,b Department of Laboratory Diagnostic and Infectious Diseases , Fondazione Policlinico Universitario Agostino Gemelli-IRCCS , Rome , Italy
| | - Cristian Piras
- c Dipartimento di Medicina Veterinaria , Università degli studi di Milano , Milano , Italy
| | - Luisa Pieroni
- d Proteomics and Metabonomics Unit , IRCCS-Fondazione Santa Lucia , Rome , Italy
| | - Maurizio Ronci
- d Proteomics and Metabonomics Unit , IRCCS-Fondazione Santa Lucia , Rome , Italy.,e Department of Medical, Oral and Biotechnological Sciences , University "G. D'Annunzio" of Chieti-Pescara , Chieti , Italy
| | - Lorenza Putignani
- f Unit of Parasitology Bambino Gesù Children's Hospital , IRCCS , Rome , Italy.,g Unit of Human Microbiome , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
| | - Paola Roncada
- h Dipartimento di Scienze della Salute , Università degli studi "Magna Græcia" di Catanzaro , Catanzaro , Italy
| | - Andrea Urbani
- a Institute of Biochemistry and Clinical Biochemistry , Università Cattolica del Sacro Cuore , Rome , Italy.,b Department of Laboratory Diagnostic and Infectious Diseases , Fondazione Policlinico Universitario Agostino Gemelli-IRCCS , Rome , Italy
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Horatz K, Giampà M, Karpov Y, Sahre K, Bednarz H, Kiriy A, Voit B, Niehaus K, Hadjichristidis N, Michels DL, Lissel F. Conjugated Polymers as a New Class of Dual-Mode Matrices for MALDI Mass Spectrometry and Imaging. J Am Chem Soc 2018; 140:11416-11423. [DOI: 10.1021/jacs.8b06637] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Kilian Horatz
- Institute of Macromolecular Chemistry, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany
- Organic Chemistry of Polymers, Technische Universität Dresden, Mommsenstrasse 4, 01062 Dresden, Germany
| | - Marco Giampà
- Center for Biotechnology and Department for Proteome and Metabolome Research, Faculty of Biology, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany
| | - Yevhen Karpov
- Institute of Macromolecular Chemistry, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany
| | - Karin Sahre
- Institute of Macromolecular Chemistry, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany
| | - Hanna Bednarz
- Center for Biotechnology and Department for Proteome and Metabolome Research, Faculty of Biology, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany
| | - Anton Kiriy
- Institute of Macromolecular Chemistry, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany
| | - Brigitte Voit
- Institute of Macromolecular Chemistry, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany
- Organic Chemistry of Polymers, Technische Universität Dresden, Mommsenstrasse 4, 01062 Dresden, Germany
| | - Karsten Niehaus
- Center for Biotechnology and Department for Proteome and Metabolome Research, Faculty of Biology, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany
| | - Nikos Hadjichristidis
- Physical Sciences and Engineering Division, KAUST Catalysis Center, Polymer Synthesis Laboratory, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Kingdom of Saudi Arabia
| | - Dominik L. Michels
- Computer, Electrical and Mathematical Sciences and Engineering Division, KAUST Visual Computing Center, Computational Sciences Group, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Kingdom of Saudi Arabia
| | - Franziska Lissel
- Institute of Macromolecular Chemistry, Leibniz-Institut für Polymerforschung Dresden e.V., Hohe Straße 6, 01069 Dresden, Germany
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Chen X, Wang T, Lin L, Wo F, Liu Y, Liang X, Ye H, Wu J. Tip-Enhanced Photoinduced Electron Transfer and Ionization on Vertical Silicon Nanowires. ACS APPLIED MATERIALS & INTERFACES 2018; 10:14389-14398. [PMID: 29648434 DOI: 10.1021/acsami.8b00506] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/08/2023]
Abstract
Nanostructured semiconductors are one of the most potent candidates for matrix-free laser desorption/ionization mass spectrometric (LDI-MS) analysis of low-molecular-weight molecules. Herein, the enhanced photoinduced electron transfer and LDI on the tip of a vertical silicon nanowire (SiNW) array were investigated. Theoretical simulation and LDI detection of indigo and isatin molecules in negative ion mode revealed that the electric field can be enhanced on the tip end of SiNWs, thereby promoting the energy and electron transfer to the analytes adsorbed on the tip of SiNWs. On the basis of this finding, a tip-contact sampling method coupled with LDI-MS detection was established. In this strategy, the tip of SiNWs can be regarded as microextraction heads for the sampling of molecules when they come in contact with analytes. Impression of skin, tissue, and pericarp on the vertical SiNW array can effectively transfer endogenous metabolites or exogenous substances onto the tip. Upon laser irradiation, the adsorbed molecules on the SiNW tip can be efficiently ionized and detected in negative ion mode because of the tip-enhanced electron transfer and LDI effect. We believe this work may significantly expand the application of LDI-MS in various fields.
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Affiliation(s)
- Xiaoming Chen
- Institute of Analytical Chemistry, Department of Chemistry , Zhejiang University , Hangzhou 310058 , P. R. China
| | - Tao Wang
- Institute of Analytical Chemistry, Department of Chemistry , Zhejiang University , Hangzhou 310058 , P. R. China
| | - Leimiao Lin
- Institute of Analytical Chemistry, Department of Chemistry , Zhejiang University , Hangzhou 310058 , P. R. China
| | - Fangjie Wo
- Institute of Analytical Chemistry, Department of Chemistry , Zhejiang University , Hangzhou 310058 , P. R. China
| | - Yaqin Liu
- Institute of Analytical Chemistry, Department of Chemistry , Zhejiang University , Hangzhou 310058 , P. R. China
| | - Xiao Liang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine , Zhejiang University , Hangzhou 310016 , P. R. China
| | - Hui Ye
- College of Optical Science and Engineering , Zhejiang University , Hangzhou 310027 , P. R. China
| | - Jianmin Wu
- Institute of Analytical Chemistry, Department of Chemistry , Zhejiang University , Hangzhou 310058 , P. R. China
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YU JJ, LIU P, ZENG Z, CHEN Y, GAO W, LI M, WANG CG, HUANG ZX, ZHOU Z, LI L. Development and Characterization of A Linear Matrix-assisted Laser Desorption Ionization Mass Spectrometer. CHINESE JOURNAL OF ANALYTICAL CHEMISTRY 2018. [DOI: 10.1016/s1872-2040(17)61077-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/01/2022]
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Deepaisarn S, Tar PD, Thacker NA, Seepujak A, McMahon AW. Quantifying biological samples using Linear Poisson Independent Component Analysis for MALDI-ToF mass spectra. Bioinformatics 2018; 34:1001-1008. [PMID: 29091994 PMCID: PMC5860625 DOI: 10.1093/bioinformatics/btx630] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2017] [Revised: 09/07/2017] [Accepted: 10/27/2017] [Indexed: 01/12/2023] Open
Abstract
Motivation Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI) facilitates the analysis of large organic molecules. However, the complexity of biological samples and MALDI data acquisition leads to high levels of variation, making reliable quantification of samples difficult. We present a new analysis approach that we believe is well-suited to the properties of MALDI mass spectra, based upon an Independent Component Analysis derived for Poisson sampled data. Simple analyses have been limited to studying small numbers of mass peaks, via peak ratios, which is known to be inefficient. Conventional PCA and ICA methods have also been applied, which extract correlations between any number of peaks, but we argue makes inappropriate assumptions regarding data noise, i.e. uniform and Gaussian. Results We provide evidence that the Gaussian assumption is incorrect, motivating the need for our Poisson approach. The method is demonstrated by making proportion measurements from lipid-rich binary mixtures of lamb brain and liver, and also goat and cow milk. These allow our measurements and error predictions to be compared to ground truth. Availability and implementation Software is available via the open source image analysis system TINA Vision, www.tina-vision.net. Contact paul.tar@manchester.ac.uk. Supplementary information Supplementary data are available at Bioinformatics online.
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Affiliation(s)
- S Deepaisarn
- Division of Informatics, Imaging and Data Sciences, The University of Manchester, UK
| | - P D Tar
- Division of Informatics, Imaging and Data Sciences, The University of Manchester, UK
| | - N A Thacker
- Division of Informatics, Imaging and Data Sciences, The University of Manchester, UK
| | - A Seepujak
- Division of Informatics, Imaging and Data Sciences, The University of Manchester, UK
| | - A W McMahon
- Division of Informatics, Imaging and Data Sciences, The University of Manchester, UK
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Neves ACO, Morais CLM, Mendes TPP, Vaz BG, Lima KMG. Mass spectrometry and multivariate analysis to classify cervical intraepithelial neoplasia from blood plasma: an untargeted lipidomic study. Sci Rep 2018; 8:3954. [PMID: 29500376 PMCID: PMC5834598 DOI: 10.1038/s41598-018-22317-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2017] [Accepted: 02/21/2018] [Indexed: 02/06/2023] Open
Abstract
Cervical cancer is still an important issue of public health since it is the fourth most frequent type of cancer in women worldwide. Much effort has been dedicated to combating this cancer, in particular by the early detection of cervical pre-cancerous lesions. For this purpose, this paper reports the use of mass spectrometry coupled with multivariate analysis as an untargeted lipidomic approach to classifying 76 blood plasma samples into negative for intraepithelial lesion or malignancy (NILM, n = 42) and squamous intraepithelial lesion (SIL, n = 34). The crude lipid extract was directly analyzed with mass spectrometry for untargeted lipidomics, followed by multivariate analysis based on the principal component analysis (PCA) and genetic algorithm (GA) with support vector machines (SVM), linear (LDA) and quadratic (QDA) discriminant analysis. PCA-SVM models outperformed LDA and QDA results, achieving sensitivity and specificity values of 80.0% and 83.3%, respectively. Five types of lipids contributing to the distinction between NILM and SIL classes were identified, including prostaglandins, phospholipids, and sphingolipids for the former condition and Tetranor-PGFM and hydroperoxide lipid for the latter. These findings highlight the potentiality of using mass spectrometry associated with chemometrics to discriminate between healthy women and those suffering from cervical pre-cancerous lesions.
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Affiliation(s)
- Ana C O Neves
- Institute of Chemistry, Biological Chemistry and Chemometrics, Federal University of Rio Grande do Norte, Natal, 59072-970, RN, Brazil
| | - Camilo L M Morais
- Institute of Chemistry, Biological Chemistry and Chemometrics, Federal University of Rio Grande do Norte, Natal, 59072-970, RN, Brazil
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, United Kingdom
| | - Thais P P Mendes
- School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, United Kingdom
| | - Boniek G Vaz
- Institute of Chemistry, Federal University of Goiás, Goiânia, 74690-900, GO, Brazil
| | - Kássio M G Lima
- Institute of Chemistry, Biological Chemistry and Chemometrics, Federal University of Rio Grande do Norte, Natal, 59072-970, RN, Brazil.
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Lu Z, Chen Y, Jing X, Hu C. Diagnostic accuracy of MALDI-TOF mass spectrometry for non-small cell lung cancer: a meta-analysis. Biomarkers 2018; 23:245-252. [PMID: 29264950 DOI: 10.1080/1354750x.2017.1420822] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Zhaolian Lu
- School of Graduate, Second Military Medical University, Shanghai, China
- Department of Laboratory Medicine, General Hospital of Jinan Military Command Region, Jinan, China
| | - Yingjian Chen
- Department of Laboratory Medicine, General Hospital of Jinan Military Command Region, Jinan, China
| | - Xinyan Jing
- School of Graduate, Weifang Medical University, Weifang, China
| | - Chengjin Hu
- Department of Laboratory Medicine, General Hospital of Jinan Military Command Region, Jinan, China
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Laser desorption/ionization MS imaging of cancer kidney tissue on silver nanoparticle-enhanced target. Bioanalysis 2018; 10:83-94. [DOI: 10.4155/bio-2017-0195] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Aim: Renal cell carcinoma is a very aggressive and often fatal disease for which there are no specific biomarkers found to date. The purpose of work was to find substances that differentiate the cancerous and healthy tissue by using laser desorption/ionization MS imaging combined with silver nanoparticle-enhanced target. Results: Ion images and comparative analysis of spectra revealed differences in intensities for several metabolites, for which their biochemical properties were discussed. Statistical analysis allowed to distinguish healthy and cancer tissue without the involvement of a pathologist. Conclusion: Laser desorption/ionization MS imaging technology combined with silver nanoparticle-enhanced target enabled rapid visualization of the differences between the clear cell renal cell carcinoma and the healthy part of the kidney tissue.
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Guran R, Vanickova L, Horak V, Krizkova S, Michalek P, Heger Z, Zitka O, Adam V. MALDI MSI of MeLiM melanoma: Searching for differences in protein profiles. PLoS One 2017; 12:e0189305. [PMID: 29220390 PMCID: PMC5722329 DOI: 10.1371/journal.pone.0189305] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2017] [Accepted: 11/23/2017] [Indexed: 12/21/2022] Open
Abstract
Background Treatment of advanced cutaneous melanoma remains challenging, and new data on melanoma biology are required. The most widely accepted criteria for the prognostic evaluation of melanoma are histopathological and clinical parameters, and the identification of additional tumor markers is thus of paramount importance. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI), an important tool in cancer research, is useful for unraveling the molecular profile of melanoma. Methodology/Principal findings In this report, we used the melanoma-bearing Libechov minipig (MeLiM), a unique animal model that allows observation of the complete spontaneous regression of invasive cutaneous melanoma, to investigate i) the differences between melanoma and healthy skin protein profiles and ii) the proteins potentially involved in spontaneous regression. The MeLiM tissues were cryosected, histologically characterized, analyzed by MALDI MSI, and immunohistologically stained. Multivariate statistical analyses of the MALDI MSI data revealed ten relevant m/z ions, of which the expression levels varied significantly among the studied MeLiM tissues. These ion peaks were used to create mass ion images/maps and visualize the differences between tumor and healthy skin specimens, as well as among histologically characterized tissue regions. Conclusions/Significance Protein profiles comprising ten statistically significant mass ion peaks useful for differentiating cutaneous melanoma and healthy skin tissues were determined. Peaks at m/z 3044, 6011, 6140 and 10180 were overexpressed in melanoma compared with healthy skin tissue. More specifically, m/z 6140 was expressed at significantly (p < 0.05) higher levels in normally growing melanoma regions than in regions with early and late spontaneous regression. This study demonstrates the clinical utility of MALDI MSI for the analysis of tissue cryosections at a molecular level.
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Affiliation(s)
- Roman Guran
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Lucie Vanickova
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
| | - Vratislav Horak
- Institute of Animal Physiology and Genetics, Academy of Sciences of the Czech Republic, v.v.i., Libechov, Czech Republic
| | - Sona Krizkova
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Petr Michalek
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Zbynek Heger
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Ondrej Zitka
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Vojtech Adam
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
- * E-mail:
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Krizkova S, Kepinska M, Emri G, Eckschlager T, Stiborova M, Pokorna P, Heger Z, Adam V. An insight into the complex roles of metallothioneins in malignant diseases with emphasis on (sub)isoforms/isoforms and epigenetics phenomena. Pharmacol Ther 2017; 183:90-117. [PMID: 28987322 DOI: 10.1016/j.pharmthera.2017.10.004] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Metallothioneins (MTs) belong to a group of small cysteine-rich proteins that are ubiquitous throughout all kingdoms. The main function of MTs is scavenging of free radicals and detoxification and homeostating of heavy metals. In humans, 16 genes localized on chromosome 16 have been identified to encode four MT isoforms labelled by numbers (MT-1-MT-4). MT-2, MT-3 and MT-4 proteins are encoded by a single gene. MT-1 comprises many (sub)isoforms. The known active MT-1 genes are MT-1A, -1B, -1E, -1F, -1G, -1H, -1M and -1X. The rest of the MT-1 genes (MT-1C, -1D, -1I, -1J and -1L) are pseudogenes. The expression and localization of individual MT (sub)isoforms and pseudogenes vary at intra-cellular level and in individual tissues. Changes in MT expression are associated with the process of carcinogenesis of various types of human malignancies, or with a more aggressive phenotype and therapeutic resistance. Hence, MT (sub)isoform profiling status could be utilized for diagnostics and therapy of tumour diseases. This review aims on a comprehensive summary of methods for analysis of MTs at (sub)isoforms levels, their expression in single tumour diseases and strategies how this knowledge can be utilized in anticancer therapy.
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Affiliation(s)
- Sona Krizkova
- Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic
| | - Marta Kepinska
- Department of Biomedical and Environmental Analysis, Faculty of Pharmacy, Wroclaw Medical University, Borowska 211, 50-556 Wroclaw, Poland
| | - Gabriella Emri
- Department of Dermatology, Faculty of Medicine, University of Debrecen, Nagyerdei krt 98, H-4032 Debrecen, Hungary
| | - Tomas Eckschlager
- Department of Paediatric Haematology and Oncology, 2nd Faculty of Medicine, Charles University, and University Hospital Motol, V Uvalu 84, CZ-150 06 Prague 5, Czech Republic
| | - Marie Stiborova
- Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, CZ-128 40 Prague 2, Czech Republic
| | - Petra Pokorna
- Department of Biochemistry, Faculty of Science, Charles University, Albertov 2030, CZ-128 40 Prague 2, Czech Republic; Department of Oncology, 2nd Faculty of Medicine, Charles University, and University Hospital Motol, V Uvalu 84, CZ-150 06 Prague 5, Czech Republic
| | - Zbynek Heger
- Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic
| | - Vojtech Adam
- Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-616 00 Brno, Czech Republic; Department of Chemistry and Biochemistry, Mendel University in Brno, Zemedelska 1, CZ-613 00 Brno, Czech Republic.
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Serafim V, Shah A, Puiu M, Andreescu N, Coricovac D, Nosyrev AE, Spandidos DA, Tsatsakis AM, Dehelean C, Pinzaru I. Classification of cancer cell lines using matrix-assisted laser desorption/ionization time‑of‑flight mass spectrometry and statistical analysis. Int J Mol Med 2017; 40:1096-1104. [PMID: 28765873 PMCID: PMC5593469 DOI: 10.3892/ijmm.2017.3083] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Accepted: 07/12/2017] [Indexed: 01/08/2023] Open
Abstract
Over the past decade, matrix-assisted laser desorption/ionization time‑of‑flight mass spectrometry (MALDI‑TOF MS) has been established as a valuable platform for microbial identification, and it is also frequently applied in biology and clinical studies to identify new markers expressed in pathological conditions. The aim of the present study was to assess the potential of using this approach for the classification of cancer cell lines as a quantifiable method for the proteomic profiling of cellular organelles. Intact protein extracts isolated from different tumor cell lines (human and murine) were analyzed using MALDI‑TOF MS and the obtained mass lists were processed using principle component analysis (PCA) within Bruker Biotyper® software. Furthermore, reference spectra were created for each cell line and were used for classification. Based on the intact protein profiles, we were able to differentiate and classify six cancer cell lines: two murine melanoma (B16‑F0 and B164A5), one human melanoma (A375), two human breast carcinoma (MCF7 and MDA‑MB‑231) and one human liver carcinoma (HepG2). The cell lines were classified according to cancer type and the species they originated from, as well as by their metastatic potential, offering the possibility to differentiate non‑invasive from invasive cells. The obtained results pave the way for developing a broad‑based strategy for the identification and classification of cancer cells.
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Affiliation(s)
- Vlad Serafim
- Center of Genomic Medicine, 'Victor Babes' University of Medicine and Pharmacy, Timisoara 300041, Romania
- Department of Natural Sciences, Middlesex University, London NW4 4BT, UK
| | - Ajit Shah
- Department of Natural Sciences, Middlesex University, London NW4 4BT, UK
| | - Maria Puiu
- Center of Genomic Medicine, 'Victor Babes' University of Medicine and Pharmacy, Timisoara 300041, Romania
| | - Nicoleta Andreescu
- Center of Genomic Medicine, 'Victor Babes' University of Medicine and Pharmacy, Timisoara 300041, Romania
| | - Dorina Coricovac
- Department of Toxicology, Faculty of Pharmacy, 'Victor Babes' University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Alexander E. Nosyrev
- Central Chemical Laboratory of Toxicology, I.M. Sechenov First Moscow State Medical University, 119991 Moscow, Russia
| | | | - Aristides M. Tsatsakis
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, 71003 Heraklion, Greece
| | - Cristina Dehelean
- Department of Toxicology, Faculty of Pharmacy, 'Victor Babes' University of Medicine and Pharmacy, 300041 Timisoara, Romania
| | - Iulia Pinzaru
- Department of Toxicology, Faculty of Pharmacy, 'Victor Babes' University of Medicine and Pharmacy, 300041 Timisoara, Romania
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Moulick A, Milosavljevic V, Nguyen HV, Kopel P, Adam V. Electrochemical Characterization of the Interaction of Multiwalled Carbon Nanotubes with Doxorubicin. ANAL LETT 2017. [DOI: 10.1080/00032719.2017.1284860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Affiliation(s)
- Amitava Moulick
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Vedran Milosavljevic
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Hoai Viet Nguyen
- Research Center for Environmental Monitoring and Modeling, University of Science – Vietnam National University, Hanoi, Vietnam
| | - Pavel Kopel
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
| | - Vojtech Adam
- Department of Chemistry and Biochemistry, Mendel University in Brno, Brno, Czech Republic
- Central European Institute of Technology, Brno University of Technology, Brno, Czech Republic
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