Cancer Metabolomics: Methods and Applications (Advances in Experimental Medicine and Biology, 1280)

"Cancer metabolomics is a rapidly evolving field that aims for a comprehensive dissection of the metabolic phenotypes and functional network of metabolites in human cancers. State of the art metabolomics tools have been developed and applied to studying cancer metabolism and developing metabolic targets for improved diagnosis, prognosis and therapeutic treatment of human cancers. Chapters are written by subject experts in the field of cancer metabolomics with cross-disciplinary contributions. Coverage includes advanced metabolomics technologies and methodologies, including chemical isotope labelling liquid chromatography - mass spectrometry, capillary ion chromatography - mass spectrometry, 2-D gas chromatography - mass spectrometry, capillary electrophoresis - mass spectrometry, nuclear magnetic resonance spectroscopy, shotgun lipidomics, tracer-based metabolomics, microbial metabolomics, mass spectrometry imaging for single cell metabolomics and functional metabolomics. In addition, the book highlights new discoveries in cancer metabolism such as hypoxia inducible factor pathway, isocitrate dehydrogenase 1 mutation and oncometabolites. Finally, contributors focus on the translational applications of metabolomics in human cancers such as glioma, head and neck cancer, and gastric cancer. This new volume will be a unique reference source for cancer researchers and promote applications of metabolomics in understanding cancer metabolism"--Publisher's description Contents Contributors About the Editor Chemical Isotope Labeling LC-MS for Metabolomics 1 LC-MS for Metabolomics: Conventional Approach 2 Stable Isotope Labeling LC-MS for Metabolomics 3 Chemical Isotope Labeling LC-MS Metabolomics Workflow 4 Derivatization Reagents for CIL LC-MS Metabolomics 5 Key Features of High-Performance CIL LC-MS 6 Multichannel CIL LC-MS Metabolome Analysis 7 Limitations and Future Direction of CIL LC-MS Metabolomics 8 Applications of CIL LC-MS for Cancer Metabolomics 9 Conclusions References NMR-Based Metabolomics 1 Metabolomics 2 Analytical Methods for Metabolomics 3 Characteristics of NMR Spectroscopy 4 Workflow for NMR-Based Metabolomics 5 Biological Samples 6 Sample Processing 6.1 Serum/Plasma 6.2 Urine 6.3 Cells and Tissues 7 NMR Experiments 7.1 1D NMR Methods 7.2 2D NMR Methods 7.3 NMR Techniques for Analysis of Mass Limited Samples 7.4 Fast Data Acquisition Methods 7.5 Ultrasensitive NMR Methods 8 Isotope Labeling Methods 8.1 Isotope Labeling in Flux Measurements 8.2 Isotope Labeling in Plants/Organisms 8.3 Ex Vivo Isotope Labeling 9 Data Analysis 9.1 Chemometric Analysis 9.1.1 Unsupervised Analysis 9.1.2 Supervised Analysis 9.2 Quantitative Analysis 9.2.1 Quantitative Analysis of Metabolites in Serum, Plasma, and Whole Blood 9.2.2 Quantitative Analysis of Major Coenzymes/Antioxidants in Blood, Tissue, and Cells 10 Summary References Mass Spectrometry-Based Shotgun Lipidomics for Cancer Research 1 Introduction 2 MS-Based Shotgun Lipidomic Approaches 2.1 Mass Spectrometers and Ionization Methods 2.2 Direct Infusion-Based Shotgun Lipidomics 2.2.1 Introduction 2.2.2 Tandem MS-Based Shotgun Lipidomics 2.2.3 High Mass Accuracy-Based Lipidomics 2.2.4 Multidimensional MS-Based Shotgun Lipidomics 2.3 Imaging Lipidomics 2.3.1 Matrix-Assisted Laser Desorption/Ionization-Mass Spectrometry Imaging 2.3.2 Desorption Electrospray Ionization Imaging 2.3.3 Secondary Ion Mass Spectrometry Imaging 3 Quantification Methods 3.1 Principles and Single-Step Quantification 3.2 Two-Step Quantification by MDMS-Based Shotgun Lipidomics 4 Bioinformatics for Shotgun Lipidomics 4.1 Lipid Identification Tools and Databases 4.2 Biostatistics and Data Interpretation 5 Application of Shotgun Lipidomics for Cancer Research 6 Summary References Comprehensive Two-Dimensional Gas Chromatography Mass Spectrometry-Based Metabolomics 1 Introduction 2 GC × GC-MS System and Its Operation 2.1 Modulator 2.2 Column Configuration 2.3 Mass Spectrometer 3 Sample Preparation for GC × GC-MS 4 Data Analysis 4.1 Spectrum Deconvolution and Metabolite Identification 4.2 Cross-Sample Alignment and Normalization 4.3 Statistical Analysis 5 Applications of GC × GC-MS in Metabolomics 6 Conclusions References Single-Cell Metabolomics by Mass Spectrometry Imaging 1 Introduction to Mass Spectrometry Imaging 2 Technological Advances in High-Spatial-Resolution MALDI-MSI 3 Mass Spectrometry Imaging for Metabolomic Analysis 4 Metabolite Identification and Localization 5 Recent Applications 6 Conclusion and Outlook References Detection of N6-Methyladenine in Eukaryotes 1 Introduction 2 LC-MS for Qualitative and Quantitative Analysis of 6mA 2.1 MS Analysis of 6mA in Oligos 2.2 Preparation of Mononucleotides by DNA Hydrolysis for LC-MS Analysis 2.3 Enhancement of the MS Signal for Released Nucleosides 2.4 Stable Isotope Labeling [15N5]-dA Tracing Veritable 6mA 2.4.1 Involvement of [15N5]-dA in the Adenine Deamination-Regulated Purine Salvage Pathway 2.4.2 Differentiation of the 6mA from Nonproliferative Prokaryotic DNA and Human DNA 2.4.3 Tracing of 6mA Origin by LC-MS with Stable Isotope Labeling 2.4.4 Undetectable [15N4]-6mA in Mouse Embryonic Stem Cells 3 Antibody-Based Assays 3.1 Enrichment of 6mA-Specific DNA Fragments by Multiple Immunoprecipitation 4 High-Throughput DNA Sequencing Technology 4.1 Next-Generation Sequence 4.2 Single-Molecule, Real-Time (SMRT) Sequencing Technology References Microbial Metabolomics: From Methods to Translational Applications 1 Introduction 2 Methods in Microbial Metabolomics 2.1 Key Analytical Tools for Microbial Metabolomics 2.2 Sample Preparation and Data Mining of Microbial Metabolomics 2.3 Biological Annotation of Differential Metabolic Pathways Characterized by Microbial Metabolomics 3 Translational Applications of Microbial Metabolomics 3.1 Diagnosis of Infectious Diseases Caused by Pathogenic Microbes 3.2 Pathogenesis Annotation of Microbial Infections 3.3 Development of Antibiotic Resistance Against Microbe-Associated Infections 3.4 Treatment of Infectious Diseases Caused by Pathogenic Microbes 4 Concluding Remarks and Future Perspective References Tracer-Based Cancer Metabolomic Analysis 1 Introduction 2 Isotope Analysis of Cancer Metabolism 2.1 13C Isotopic Tracer 2.2 15N Isotopic Tracer 2.3 2H Isotope Tracer 3 Flux Measurement 3.1 Glycolysis/Lactic Fermentation 3.2 Pentose Phosphate Pathway 3.3 Pyruvate Cycling 3.4 TCA Cycle and Glutaminolysis 3.5 De Novo Lipogenesis 4 NMR-Based Isotope Tracer Analysis 4.1 NMR-Based Isotope Tracing Methodology 4.2 Applications of NMR-Based Isotope Analysis 5 MS-Based Isotope Analysis 5.1 LC-MS-Based Isotope Analysis 5.2 GC-MS-Based Isotope Analysis 6 Combined Analysis of NMR and MS Spectra (CANMS) 7 Conclusions References Functional Metabolomics and Chemoproteomics Approaches Reveal Novel Metabolic Targets for Anticancer Therapy 1 Introduction 2 Metabolomics in Anticancer Target Discovery 2.1 Essential Procedures and Advancements of Metabolomics Technologies 2.1.1 Sample Collection and Preparation 2.1.2 Metabolomic Acquisition Methods and Data Analysis Tools 2.1.3 Innovative Metabolomics Data Analysis Approaches 2.2 Metabolomics for Biomarker Discovery and Therapeutic Target Identification 2.2.1 Metabolomics in Metabolic Biomarker and Target Discovery 2.2.2 Metabolomics in Cancer Chemotherapy 3 Combined Metabolomics and Proteomics in Cancer Metabolic Target Discovery 4 Novel Chemoproteomics-Based Approach for Direct Target Identification 5 Conclusion References Ion Chromatography with Mass Spectrometry for Metabolomic Analysis 1 Principle of Ion Chromatography 2 Advantages of IC Separation 3 Stationary Phase in IC 4 Mobile Phase in IC 5 Detection Modes in IC 6 Application of IC-MS for Metabolomic Analysis 7 Conclusion References Quantitative Analysis of Oncometabolite 2-Hydroxyglutarate 1 Introduction 2 Methods for Quantitative Analysis of 2HG 2.1 LC-MS-Based Detection of 2HG 2.2 Chiral LC-MS-Based Detection of D-2HG and L-2HG 2.3 Chiral Derivatization with LC-MS for the Detection of D-2HG and L-2HG 2.4 GC-MS-Based Detection of 2HG 2.5 Chiral GC-MS-Based Detection of D-2HG and L-2HG 2.6 Chiral Derivatization with GC-MS for the Detection of D-2HG and L-2HG 2.7 DESI-MS-Based Detection of 2HG 2.8 Magnetic Resonance Spectroscopy (MRS)-Based Detection of D-2HG 2.9 Enzymatic Assay–Based Detection of D-2HG 3 Conclusions References Methods of Lipidomic Analysis: Extraction, Derivatization, Separation, and Identification of Lipids 1 Sample Collection and Extraction 1.1 Sample Collection 1.2 Sample Extraction 1.2.1 Liquid–Liquid Extraction (LLE) 1.2.2 Solid-Phase Extraction (SPE) 1.2.3 Solid-Phase Microextraction (SPME) 1.2.4 Emerging Techniques for Lipid Extraction 2 Derivatization 2.1 Advantages of Derivatization 2.2 Lipid Analysis After Derivatization 3 Chromatographic Methods 3.1 Thin-Layer Chromatography (TLC) 3.2 GC Separation of Lipids 3.3 LC Separation of Lipids 3.3.1 RPLC 3.3.2 NPLC and HILIC 3.3.3 SFC 4 MS Analysis of Lipids 4.1 Ionization Methods 4.2 MS Detection 5 Quality Control 6 Data Processing and Analysis 6.1 Spectral Data Processing 6.2 Annotation of Lipid Species 6.3 Bioinformatics Tools for Lipidomic Data Processing 6.4 Biostatistical Analysis and Data Visualization References Capillary Electrophoresis-Mass Spectrometry for Cancer Metabolomics 1 Introduction 2 Capillary Electrophoresis with Mass Spectrometry 2.1 Separation Modes of Capillary Electrophoresis 2.1.1 Capillary Zone Electrophoresis 2.1.2 Micellar Electrokinetic Chromatography 2.1.3 Nonaqueous Capillary Electrophoresis 2.1.4 Capillary Gel Electrophoresis 2.1.5 Capillary Isoelectric Focusing 2.1.6 Capillary Electrochromatography 2.1.7 Capillary Isotachophoresis 2.2 CE Interface with MS 2.2.1 Sheath-Flow Interface 2.2.2 Sheathless Interface 2.3 Capillary Coating 2.4 Sample Preparation in CE-MS-Based Metabolomic Analysis 3 Applications of CE-MS in Cancer Metabolomics 4 Conclusion and Perspective References NMR-Based Metabolomics in Cancer Research 1 Introduction 2 NMR-Based Metabolomic Approach 2.1 Experimental Design and Sample Collection 2.2 Sample Preparation and Data Acquisition 2.3 Metabolite Assignment and Data Analysis 2.4 Interpretation and Validation 3 NMR-Based Cancer Metabolomics 3.1 Biofluids 3.2 Stool Samples 3.3 Cell Line Models 3.4 Cancer Tissues 4 Challenge and Innovation 4.1 Sample Preparation 4.2 High-Resolution Microcoil NMR 4.3 LC with NMR 4.4 Optimization of Data Processing 5 Conclusion References Regulation of Glycolysis in Head and Neck Cancer 1 Introduction 2 Glucose Metabolism in HNSCC 2.1 Hypoxia Inducible Factor-1 2.2 Glucose Transporter-1 2.3 Hexokinase-II 2.4 Lactate Dehydrogenase A 2.5 Pyruvate Kinase M2 2.6 Monocarboxylate Transports 3 Signaling Pathways in HNSCC Glucose Metabolism 3.1 Akt Signaling 3.2 EGFR Signaling 3.3 HIF-1 Signaling 3.4 NOTCH Signaling 3.5 JAK/STAT Signaling 3.6 Hepatocyte Growth Factor/c-Met Signaling 4 Role of Tumor Microenvironment in HNSCC Metabolism 5 Therapeutic Interventions for Targeting HNSCC Metabolism 6 Conclusion and Future Prospective References Fatty Acid Metabolism and Cancer 1 Fatty Acid Metabolism 2 Fatty Acid Synthesis in Cancer 2.1 Regulation of Fatty Acid Synthesis in Cancer 2.2 Targeting Fatty Acid Synthesis in Cancer 3 Fatty Acid Oxidation in Cancer 4 Clinical Perspective References HIF-1α Metabolic Pathways in Human Cancer 1 Hypoxic Response 2 Hypoxia-Inducible Factor 2.1 Discovery of HIF-1 2.2 Regulation of HIF-1α 2.3 HIF-1α Stability 3 HIF-1α and Metabolic Reprogramming 4 Hypoxia and Cancer 5 HIF-1α and Immune Cells in Cancer 6 Role of HIF-1α in Key Cancer Pathways 6.1 Cell Adhesion 6.2 Cell Proliferation 6.3 Metastasis and Invasion 6.4 Angiogenesis 6.5 Apoptosis 7 Clinical Significance and HIF-1α Inhibitors for Cancer Therapy 8 Conclusion References Metabolomics of Glioma 1 Introduction 2 Recent Advances in Metabolic Pathways of Glioma 2.1 IDH1/2 Gene Mutation 2.1.1 IDH1/2 Mutation and Glioma 2.1.2 IDH1/2 Mutation and 2-HG 2.1.3 Metabolomic Alterations in IDH Mutant Cells 2.2 Other Metabolic Pathways in Glioma 2.2.1 Amino Acid Metabolism 2.2.2 Nucleotide Metabolism 2.2.3 Lipid Metabolism 3 Metabolomic Analysis of Glioma 3.1 Cerebrospinal Fluids 3.2 Plasma and Serum 3.3 Glioma Tissues 4 Application of Metabolomics in Glioma 4.1 Diagnosis of Glioma 4.2 Prognosis of Glioma 4.3 Treatment of Glioma 5 Conclusion and Future Prospective References Metabolomics of Oral/Head and Neck Cancer 1 Introduction 1.1 Oral/Head and Neck Cancer 1.1.1 Symptoms 1.1.2 Diagnosis 1.1.3 Treatment 1.2 Metabolomics 1.3 Application of Metabolomics in Cancer Research 2 Body Fluid Metabolomics in OSCC/HNSCC 2.1 Saliva Metabolomics 2.2 Serum Metabolomics 2.3 Urine Metabolomics 3 Metabolomic Analysis of OSCC/HNSCC Cell Lines and Tissues 4 Conclusion References Metabolomics of Gastric Cancer 1 Introduction 1.1 Metabolomics 1.2 Gastric Cancer 2 Recent Advances in Gastric Cancer Metabolism 2.1 Glucose Metabolism 2.2 Amino Acid Metabolism 2.3 Lipid Metabolism 2.4 Nucleotide Metabolism 2.5 Other Metabolisms in Gastric Cancer 3 Metabolomic Analysis of Gastric Cancer 3.1 Diagnosis 3.2 Prognosis 3.3 Treatment 4 Conclusion and Future Perspective References Index Chemical isotope labeling LC-MS for metabolomics / Shuang Zhao and Liang Li -- NMR-based metabolomics / G.A. Nagana Gowda and Daniel Raftery -- Mass spectrometry-based shotgun lipidomics for cancer research / Jianing Wang, Chunyan Wang, and Xianlin Han -- Comprehensive two-dimensional gas chromatography mass spectrometry-based metabolomics / Md Aminul Islam Prodhan, Craig McClain, and Xiang Zhang -- Single-cell metabolomics by mass spectrometry imaging / Maria Emilia Dueñas and Young Jin Lee -- Detection of N6-methyladenine in eukaryotes / Baodong Liu and Hailin Wang -- Microbial metabolomics: from methods to translational applications / Rui Guo [and 5 others] -- Tracer-based cancer metabolomic analysis / Jianzhou Liu, Jing Huang, and Gary Guishan Xiao -- Functional metabolomics and chemoproteomics approaches reveal novel metabolic targets for anticancer therapy / Chang Shao [and 3 others] -- Ion chromatography with mass spectrometry for metabolomic analysis / Eoon Hye Ji, Jason Lee, and Shen Hu -- Quantitative analysis of oncometabolite 2-hydroxyglutarate / Bi-Feng Yuan -- Methods of lipidomic analysis: extraction, derivatization, separation, and identification of lipids / Ya Xie [and 6 others] -- Capillary electrophoresis-mass spectrometry for cancer metabolomics / Xiangdong Xu -- NMR-based metabolomics in cancer research / Rui Hu [and 4 others] -- Regulation of glycolysis in head and neck cancer / Sibi Raj, Ashok Kumar, and Dhruv Kumar -- Fatty acid metabolism and cancer / Zhenning Jin, Yang D. Chai, and Shen Hu -- HIF-1[alpha] metabolic pathways in human cancer / Naseim Elzakra and Yong Kim -- Metabolomics of glioma / Sizhe Feng and Yutong Liu -- Metabolomics of oral/head and neck cancer / Gaofei Yin [and 3 others] -- Metabolomics of gastric cancer / Wroocha Kadam, Bowen Wei, and Feng Li -- Index