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Rong Y, Teng Y, Zhou X. Advances in the Study of Metabolic Reprogramming in Gastric Cancer. Cancer Med 2025; 14:e70948. [PMID: 40365984 PMCID: PMC12076355 DOI: 10.1002/cam4.70948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Revised: 02/18/2025] [Accepted: 04/29/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Gastric cancer is one of the most prevalent malignancies of the digestive system and is associated with a poor prognosis, particularly in advanced metastatic stages, where the 5-year survival rate is significantly low. METHODS Recent research has demonstrated that metabolic reprogramming-including alterations in glucose, lipid, and amino-acid metabolism-plays a critical role in both the development and progression of this disease. To gain deeper insights into these metabolic shifts, scientists have increasingly employed metabolomics, a non-invasive technique that detects and quantifies small molecules within cancerous tissues, thereby enhancing prognostic assessments. AIM Analyzing the metabolic profiles of gastric-cancer tissues can reveal significant changes in key metabolic pathways, which may open new avenues for targeted therapies and ultimately improve patient outcomes. CONCLUSION This article reviews recent advancements in the study of metabolic reprogramming in gastric cancer, aiming to identify potential therapeutic targets and offer new hope to patients.
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Affiliation(s)
- Yu Rong
- The First Clinical Medical College, Nanjing Medical UniversityNanjingChina
| | - Yuanyin Teng
- The Second Clinical Medical College, Nanjing Medical UniversityNanjingChina
| | - Xiaoying Zhou
- The First Clinical Medical College, Nanjing Medical UniversityNanjingChina
- Department of GastroenterologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
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Dai Q, Liu Y, Ding F, Guo R, Cheng G, Wang H. CircRNAs: A promising target for intervention regarding glycolysis in gastric cancer. Heliyon 2024; 10:e34658. [PMID: 39816354 PMCID: PMC11734058 DOI: 10.1016/j.heliyon.2024.e34658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 07/12/2024] [Accepted: 07/14/2024] [Indexed: 01/18/2025] Open
Abstract
Gastric cancer is characterized by a high incidence and mortality rate, with therapeutic efficacy currently constrained by substantial limitations. Aerobic glycolysis in cancer constitutes a pivotal aspect of the reprogramming of energy metabolism in tumor cells and profoundly influences the malignant progression of cancer. CircRNAs, serving as stable endogenous RNA, have been shown to regulate downstream targets by sponging miRNAs, which in turn are involved in the regulation of multiple malignant behaviors in a variety of cancers through the CircRNA-miRNA axis, suggesting that CircRNAs could be used as potential therapeutic targets for cancer. In recent years, it has been shown that some CircRNAs can be involved in the regulation of GC glycolysis, therefore, this paper summarizes the notable roles of some important CircRNAs in the regulation of GC glycolysis in recent years, which may be useful for our understanding of GC progression and the development of new therapeutic strategies.
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Affiliation(s)
- Qian Dai
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
| | - Yulin Liu
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Fanghui Ding
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
| | - Rong Guo
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Gang Cheng
- The Second Clinical Medical College, Lanzhou University, Lanzhou, China, 730000
| | - Hua Wang
- The First Hospital of Lanzhou University, Lanzhou, China, 730000
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3
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Balonov I, Mattis M, Jarmusch S, Koletzko B, Heinrich K, Neumann J, Werner J, Angele MK, Heiliger C, Jacob S. Metabolomic profiling of upper GI malignancies in blood and tissue: a systematic review and meta-analysis. J Cancer Res Clin Oncol 2024; 150:331. [PMID: 38951269 PMCID: PMC11217139 DOI: 10.1007/s00432-024-05857-5] [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: 05/10/2024] [Accepted: 06/17/2024] [Indexed: 07/03/2024]
Abstract
OBJECTIVE To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.
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Affiliation(s)
- Ilja Balonov
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Minca Mattis
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Stefanie Jarmusch
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Berthold Koletzko
- Division of Metabolic and Nutritional Medicine, Dr. Von Hauner Children's Hospital, Ludwig-Maximilians-University Munich Medical Center, Lindwurmstraße 4, 80337, Munich, Germany
| | - Kathrin Heinrich
- Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
| | - Jens Neumann
- Institute of Pathology, Ludwig-Maximilians-University (LMU) Munich, Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Martin K Angele
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Christian Heiliger
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - Sven Jacob
- Department of General, Visceral and Transplantation Surgery, University Hospital, LMU Munich, Ludwig-Maximilians-University (LMU) Munich, Marchioninistr. 15, 81377, Munich, Germany.
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4
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Li J, Xu S, Zhu F, Shen F, Zhang T, Wan X, Gong S, Liang G, Zhou Y. Multi-omics Combined with Machine Learning Facilitating the Diagnosis of Gastric Cancer. Curr Med Chem 2024; 31:6692-6712. [PMID: 38351697 DOI: 10.2174/0109298673284520240112055108] [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: 09/27/2023] [Revised: 11/28/2023] [Accepted: 01/03/2024] [Indexed: 10/19/2024]
Abstract
Gastric cancer (GC) is a highly intricate gastrointestinal malignancy. Early detection of gastric cancer forms the cornerstone of precision medicine. Several studies have been conducted to investigate early biomarkers of gastric cancer using genomics, transcriptomics, proteomics, and metabolomics, respectively. However, endogenous substances associated with various omics are concurrently altered during gastric cancer development. Furthermore, environmental exposures and family history can also induce modifications in endogenous substances. Therefore, in this study, we primarily investigated alterations in DNA mutation, DNA methylation, mRNA, lncRNA, miRNA, circRNA, and protein, as well as glucose, amino acid, nucleotide, and lipid metabolism levels in the context of GC development, employing genomics, transcriptomics, proteomics, and metabolomics. Additionally, we elucidate the impact of exposure factors, including HP, EBV, nitrosamines, smoking, alcohol consumption, and family history, on diagnostic biomarkers of gastric cancer. Lastly, we provide a summary of the application of machine learning in integrating multi-omics data. Thus, this review aims to elucidate: i) the biomarkers of gastric cancer related to genomics, transcriptomics, proteomics, and metabolomics; ii) the influence of environmental exposure and family history on multiomics data; iii) the integrated analysis of multi-omics data using machine learning techniques.
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Affiliation(s)
- Jie Li
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Siyi Xu
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Feng Zhu
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
| | - Fei Shen
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
| | - Tianyi Zhang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Xin Wan
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Saisai Gong
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
| | - Geyu Liang
- Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, Jiangsu, China
- Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Public Health, Southeast University, Nanjing, 210009, China
| | - Yonglin Zhou
- Physical and Chemical Laboratory, Jiangsu Provincial Center for Disease Control & Prevention, 172 Jiangsu Rd, Nanjing, 210009, China
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Sequeira-Antunes B, Ferreira HA. Urinary Biomarkers and Point-of-Care Urinalysis Devices for Early Diagnosis and Management of Disease: A Review. Biomedicines 2023; 11:biomedicines11041051. [PMID: 37189669 DOI: 10.3390/biomedicines11041051] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/10/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
Biosensing and microfluidics technologies are transforming diagnostic medicine by accurately detecting biomolecules in biological samples. Urine is a promising biological fluid for diagnostics due to its noninvasive collection and wide range of diagnostic biomarkers. Point-of-care urinalysis, which integrates biosensing and microfluidics, has the potential to bring affordable and rapid diagnostics into the home to continuing monitoring, but challenges still remain. As such, this review aims to provide an overview of biomarkers that are or could be used to diagnose and monitor diseases, including cancer, cardiovascular diseases, kidney diseases, and neurodegenerative disorders, such as Alzheimer’s disease. Additionally, the different materials and techniques for the fabrication of microfluidic structures along with the biosensing technologies often used to detect and quantify biological molecules and organisms are reviewed. Ultimately, this review discusses the current state of point-of-care urinalysis devices and highlights the potential of these technologies to improve patient outcomes. Traditional point-of-care urinalysis devices require the manual collection of urine, which may be unpleasant, cumbersome, or prone to errors. To overcome this issue, the toilet itself can be used as an alternative specimen collection and urinalysis device. This review then presents several smart toilet systems and incorporated sanitary devices for this purpose.
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Lopes C, Chaves J, Ortigão R, Dinis‐Ribeiro M, Pereira C. Gastric cancer detection by non-blood-based liquid biopsies: A systematic review looking into the last decade of research. United European Gastroenterol J 2022; 11:114-130. [PMID: 36461757 PMCID: PMC9892482 DOI: 10.1002/ueg2.12328] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 09/21/2022] [Indexed: 12/04/2022] Open
Abstract
Gastric cancer (GC) screening is arguable in most Western countries. Liquid biopsies are a great promise to answer the unmet need for less invasive diagnostic biomarkers in GC. Thus, we aimed at systematically reviewing the current knowledge on liquid biopsy-based biomarkers in GC screening. A systematic search on PubMed/MEDLINE and Scopus databases was performed on published articles reporting the use of non-blood specimen (saliva, gastric juice [GJ], urine and stool) on GC diagnosis. 3208 records were retrieved by June 2022. After removal of duplicate records, 2379 abstracts were screened, and 84 full texts included in this systematic review. More than 90% of studies were reported on Asian populations. Overall, 9 studies explored stool-, 12 saliva-, and 29 urine-derived biomarkers for GC detection. Additionally, 37 studies, representing the majority, analyzed GJ, focusing on nucleic acid molecules. Several miRNAs and lncRNA molecules have been associated with GC risk, particularly miR-21 (area under the curve [AUC] = 0.97, 95% CI: 0.94-1.00). Considering salivary biomarkers, the best described model in validation sets included the soybean agglutinin and Vicia villosa agglutinin lectins (AUC = 0.89, 95% CI: 0.80-0.99). Most studies in urine carried out metabolomic approaches, with two discriminatory models presenting AUC values superior to 0.97. This systematic review emphasizes the potential role of non-blood-based biomarkers, although further validation, particularly in Western countries, is mandatory, namely for non-invasive screening and/or monitoring, as well as the use of GJ as a tool to enhance upper gastrointestinal endoscopy accuracy.
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Affiliation(s)
- Catarina Lopes
- Precancerous Lesions and Early Cancer Management GroupResearch Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group)Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC)PortoPortugal,CINTESIS – Center for Health Technology and Services ResearchUniversity of PortoPortoPortugal,ICBAS‐UP – Institute of Biomedical Sciences Abel SalazarUniversity of PortoPortoPortugal
| | - Jéssica Chaves
- Precancerous Lesions and Early Cancer Management GroupResearch Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group)Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC)PortoPortugal,Department of GastroenterologyPortuguese Oncology Institute of PortoPortoPortugal
| | - Raquel Ortigão
- Precancerous Lesions and Early Cancer Management GroupResearch Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group)Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC)PortoPortugal,Department of GastroenterologyPortuguese Oncology Institute of PortoPortoPortugal
| | - Mário Dinis‐Ribeiro
- Precancerous Lesions and Early Cancer Management GroupResearch Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group)Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC)PortoPortugal,Department of GastroenterologyPortuguese Oncology Institute of PortoPortoPortugal
| | - Carina Pereira
- Precancerous Lesions and Early Cancer Management GroupResearch Center of IPO Porto (CI‐IPOP)/Rise@CI‐IPOP (Health Research Group)Portuguese Institute of Oncology of Porto (IPO Porto)/Porto Comprehensive Cancer Center (Porto.CCC)PortoPortugal,CINTESIS – Center for Health Technology and Services ResearchUniversity of PortoPortoPortugal
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7
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Piestansky J, Olesova D, Matuskova M, Cizmarova I, Chalova P, Galba J, Majerova P, Mikus P, Kovac A. Amino acids in inflammatory bowel diseases: Modern diagnostic tools and methodologies. Adv Clin Chem 2022; 107:139-213. [PMID: 35337602 DOI: 10.1016/bs.acc.2021.07.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Amino acids are crucial building blocks of living organisms. Together with their derivatives, they participate in many intracellular processes to act as hormones, neuromodulators, and neurotransmitters. For several decades amino acids have been studied for their potential as markers of various diseases, including inflammatory bowel diseases. Subsequent improvements in sample pretreatment, separation, and detection methods have enabled the specific and very sensitive determination of these molecules in multicomponent matrices-biological fluids and tissues. The information obtained from targeted amino acid analysis (biomarker-based analytical strategy) can be further used for early diagnostics, to monitor the course of the disease or compliance of the patients. This review will provide an insight into current knowledge about inflammatory bowel diseases, the role of proteinogenic amino acids in intestinal inflammation and modern analytical techniques used in its diagnosis and disease activity monitoring. Current advances in the analysis of amino acids focused on sample pretreatment, separation strategy, or detection methods are highlighted, and their potential in clinical laboratories is discussed. In addition, the latest clinical data obtained from the metabolomic profiling of patients suffering from inflammatory bowel diseases are summarized with a focus on proteinogenic amino acids.
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Affiliation(s)
- Juraj Piestansky
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia; Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Dominika Olesova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Michaela Matuskova
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Ivana Cizmarova
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Petra Chalova
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Jaroslav Galba
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Petra Majerova
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Peter Mikus
- Department of Pharmaceutical Analysis and Nuclear Pharmacy, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia; Toxicological and Antidoping Center, Faculty of Pharmacy, Comenius University in Bratislava, Bratislava, Slovakia
| | - Andrej Kovac
- Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
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Li D, Yan L, Lin F, Yuan X, Yang X, Yang X, Wei L, Yang Y, Lu Y. Urinary Biomarkers for the Noninvasive Detection of Gastric Cancer. J Gastric Cancer 2022; 22:306-318. [DOI: 10.5230/jgc.2022.22.e28] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 08/01/2022] [Accepted: 08/16/2022] [Indexed: 12/24/2022] Open
Affiliation(s)
- Dehong Li
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Li Yan
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Fugui Lin
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Xiumei Yuan
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Xingwen Yang
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Xiaoyan Yang
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Lianhua Wei
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Yang Yang
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
| | - Yan Lu
- Gansu Provincial Clinical Research Center for Laboratory Medicine, Lanzhou, China
- Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, China
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9
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Zhang MJ, Zhao JH, Tang YS, Meng FY, Gao SQ, Han S, Hou SY, Liu LY. Quantification of carbohydrates in human serum using gas chromatography–mass spectrometry with the stable isotope-labeled internal standard method. NEW J CHEM 2022; 46:11357-11367. [DOI: 10.1039/d2nj01243j] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/31/2025]
Abstract
Comparison of two derivatization approaches (silylation and acylation) for carbohydrate separation based on optimizing reaction conditions by artificial neural networks.
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Affiliation(s)
- Ming-Jia Zhang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Bionian Road, Nan gang District, Harbin, P. R. China
| | - Jin-Hui Zhao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Bionian Road, Nan gang District, Harbin, P. R. China
| | - Ying-Shu Tang
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Bionian Road, Nan gang District, Harbin, P. R. China
| | - Fan-Yu Meng
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Bionian Road, Nan gang District, Harbin, P. R. China
| | - Si-Qi Gao
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Bionian Road, Nan gang District, Harbin, P. R. China
| | - Su Han
- Department of Parasitology, Harbin Medical University, Harbin, P. R. China
| | - Shao-Ying Hou
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Bionian Road, Nan gang District, Harbin, P. R. China
| | - Li-Yan Liu
- Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Bionian Road, Nan gang District, Harbin, P. R. China
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10
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Huang S, Guo Y, Li Z, Zhang Y, Zhou T, You W, Pan K, Li W. A systematic review of metabolomic profiling of gastric cancer and esophageal cancer. Cancer Biol Med 2021; 17:181-198. [PMID: 32296585 PMCID: PMC7142846 DOI: 10.20892/j.issn.2095-3941.2019.0348] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Accepted: 12/03/2019] [Indexed: 12/13/2022] Open
Abstract
Objective: Upper gastrointestinal (UGI) cancers, predominantly gastric cancer (GC) and esophageal cancer (EC), are malignant tumor types with high morbidity and mortality rates. Accumulating studies have focused on metabolomic profiling of UGI cancers in recent years. In this systematic review, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with GC and EC. Methods: A systematic search of three databases (Embase, PubMed, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of GC and EC was conducted. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included articles. Results: A total of 52 original studies were included for review. A number of metabolites were differentially distributed between GC and EC cases and non-cases, including those involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and protein and lipid metabolism. Lactic acid, glucose, citrate, and fumaric acid were among the most frequently reported metabolites of cellular respiration while glutamine, glutamate, and valine were among the most commonly reported amino acids. The lipid metabolites identified previously included saturated and unsaturated free fatty acids, aldehydes, and ketones. However, the key findings across studies to date have been inconsistent, potentially due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. Conclusions: Studies on metabolomics have thus far provided insights into etiological factors and biomarkers for UGI cancers, supporting the potential of applying metabolomic profiling in cancer prevention and management efforts.
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Affiliation(s)
- Sha Huang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yang Guo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Zhexuan Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yang Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Tong Zhou
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Weicheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Kaifeng Pan
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Wenqing Li
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, China.,Joint International Research Center of Translational and Clinical Research, Beijing 100142, China
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11
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Xiong Z, Lin Y, Yu Y, Zhou X, Fan J, Rog CJ, Cai K, Wang Z, Chang Z, Wang G, Tao K, Cai M. Exploration of Lipid Metabolism in Gastric Cancer: A Novel Prognostic Genes Expression Profile. Front Oncol 2021; 11:712746. [PMID: 34568042 PMCID: PMC8457048 DOI: 10.3389/fonc.2021.712746] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 08/11/2021] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Alterations in lipid metabolism are increasingly being recognized. However, the application of lipid metabolism in the prognosis of gastric cancer (GC) has not yet been explored. METHODS A total of 204 lipid metabolism relative genes were analyzed in the GC cohort from The Cancer Genome Atlas (TCGA), and four independent cohorts from Gene Expression Omnibus (GEO) and one cohort from Wuhan Union Hospital were applied for external validation. Differential expression and enrichment analyses were performed between GC and normal tissue. The LASSO-Cox proportional hazard regression model was applied to select prognostic genes and to construct a gene expression profile. RESULTS Our research indicated that higher expression level of AKR1B1, PLD1, and UGT8 were correlated with worse prognosis of GC patients, while AGPAT3 was correlated with better prognosis. Furthermore, we developed a gene profile composed of AGPAT3, AKR1B1, PLD1, and UGT8 suggested three groups with a significant difference in overall survival (OS). The profile was successfully validated in an independent cohort and performed well in the immunohistochemical cohort. Furthermore, we found that ether lipid metabolism, glycerophospholipid metabolism, and glycerolipid metabolism were upregulated, and fatty acid β-oxidation and other lipid peroxidation processes were reduced in GC. CONCLUSION Collectively, we found lipid metabolism is reliable and clinically applicable in predicting the prognosis of GC based on a novel gene profile.
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Affiliation(s)
- Zhen Xiong
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yao Lin
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yan Yu
- Department of Breast and Thyroid Surgery, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xianghui Zhou
- Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jun Fan
- Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Colin J. Rog
- Department of General Surgery, Swedish Medical Center, Seattle, WA, United States
| | - Kailin Cai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zheng Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Zhijie Chang
- State Key Laboratory of Membrane Biology, School of Medicine, Tsinghua University, Beijing, China
| | - Guobin Wang
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Kaixiong Tao
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Ming Cai
- Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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12
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Huang R, Shen K, He Q, Hu Y, Sun C, Guo C, Pan Y. Metabolic Profiling of Urinary Chiral Amino-Containing Biomarkers for Gastric Cancer Using a Sensitive Chiral Chlorine-Labeled Probe by HPLC-MS/MS. J Proteome Res 2021; 20:3952-3962. [PMID: 34229439 DOI: 10.1021/acs.jproteome.1c00267] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Screening of characteristic biomarkers from chiral amino-containing metabolites in biological samples is difficult and important for the noninvasive diagnosis of gastric cancer (GC). Here, an enantiomeric pair of chlorine-labeled probes d-BPCl and l-BPCl was synthesized to selectively label d- and l-amino-containing metabolites in biological samples, respectively. Incorrect structural annotations were excluded according to the characteristic 3:1 abundance ratio of natural chlorine isotopes (35Cl and 37Cl) derived from the probes. A sensitive C18 HPLC-QQQ-MS/MS method in combination with the probes was then developed and applied in metabolomic analysis of amino-containing metabolites in urine samples. A total of 161 amino-containing metabolites were rapidly separated and determined, and 28 chiral amino acids and achiral glycine were quantified with good precision and accuracy. A total of 18 differential variables were discriminated by analyzing chiral amino-containing metabolites in urine samples of the GC patient and healthy person using the probe-based HPLC-MS/MS-MRM method combined with the orthogonal partial least squares discriminant analysis and Mann-Whitney U test with false discovery rate correction for multiple hypotheses. A diagnostic regression model including d-isoleucine, d-serine, and β-(pyrazol-1-yl)-l-alanine and age was then constructed with an average prediction correctness of 88.9% in the validation set. This work established a close connection between gastric cancer and chiral amino-containing metabolites. The mass spectrometry data analyzed in the study are publicly available via Mendeley Data (DOI: 10.17632/4bd93j9yrr.1).
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Affiliation(s)
- Rongrong Huang
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Kexin Shen
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Quan He
- Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, China
| | - Yiqiu Hu
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China
| | - Cuirong Sun
- College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Cheng Guo
- Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China
| | - Yuanjiang Pan
- Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, China
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13
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Aftabi Y, Soleymani J, Jouyban A. Efficacy of Analytical Technologies in Metabolomics Studies of the Gastrointestinal Cancers. Crit Rev Anal Chem 2021; 52:1593-1605. [PMID: 33757389 DOI: 10.1080/10408347.2021.1901646] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
According to the reports of the World Health Organization and the International Agency for Research on Cancer, cancer is the second leading cause of human death worldwide. However, early-stage detection of cancers can efficiently enhance the chance of therapy and saving lives. Metabolomics strategies apply a variety of approaches to discover new potential diagnoses, prognoses, and/or therapeutic biomarkers of various diseases. Metabolomics aims to identify and measure different low-molecular-weight biomolecules in physiological environments. In these studies, special metabolites are extracted from biological samples and identified using analytical techniques. Afterward, using data processing programs discovering significantly associated biomarkers is pursued. In the present review, we aimed to discuss recently reported analytical approaches on the metabolomics studies of gastrointestinal cancers including gastric, colorectal, and esophageal cancers. The gas- and liquid-chromatography with different detectors have been shown that are the main analytical techniques and for metabolites quantification, nuclear magnetic resonance has been utilized as a master method.
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Affiliation(s)
- Younes Aftabi
- Tuberculosis and Lung Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jafar Soleymani
- Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.,Liver and Gastrointestinal Diseases Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abolghasem Jouyban
- Pharmaceutical Analysis Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.,Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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14
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Kwon HN, Lee H, Park JW, Kim YH, Park S, Kim JJ. Screening for Early Gastric Cancer Using a Noninvasive Urine Metabolomics Approach. Cancers (Basel) 2020; 12:cancers12102904. [PMID: 33050308 PMCID: PMC7599479 DOI: 10.3390/cancers12102904] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 09/25/2020] [Accepted: 10/01/2020] [Indexed: 02/07/2023] Open
Abstract
Simple Summary There are currently no effective specific biomarkers for the screening of early gastric cancer. Recently, metabolomics has been used to profile small endogenous metabolites, demonstrating significant potential in the diagnosis/screening of cancer, owing to its ability to conduct a noninvasive sample analysis. Here, we performed a urine metabolomics analysis in the context of an early diagnosis of gastric cancer. This approach showed very high diagnostic sensitivity and specificity and performed significantly better than the analysis of serum tumor markers modalities. An additional genomic data analysis revealed the up-regulation of several genes in gastric cancer. This metabolomics-based early diagnosis approach may have the potential for mass screening an average-risk population and may facilitate endoscopic examination through risk stratification. Abstract The early detection of gastric cancer (GC) could decrease its incidence and mortality. However, there are currently no accurate noninvasive markers for GC screening. Therefore, we developed a noninvasive diagnostic approach, employing urine nuclear magnetic resonance (NMR) metabolomics, to discover putative metabolic markers associated with GC. Changes in urine metabolite levels during oncogenesis were evaluated using samples from 103 patients with GC and 100 age- and sex-matched healthy controls. Approximately 70% of the patients with GC (n = 69) had stage I GC, with the majority (n = 56) having intramucosal cancer. A multivariate statistical analysis of the urine NMR data well discriminated between the patient and control groups and revealed nine metabolites, including alanine, citrate, creatine, creatinine, glycerol, hippurate, phenylalanine, taurine, and 3-hydroxybutyrate, that contributed to the difference. A diagnostic performance test with a separate validation set exhibited a sensitivity and specificity of more than 90%, even with the intramucosal cancer samples only. In conclusion, the NMR-based urine metabolomics approach may have potential as a convenient screening method for the early detection of GC and may facilitate consequent endoscopic examination through risk stratification.
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Affiliation(s)
- Hyuk Nam Kwon
- College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea;
- Stem Cells and Metabolism Research Program, Faculty of Medicine/Helsinki Institute of Life Science, University of Helsinki, FIN-00014 Helsinki, Finland
| | - Hyuk Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (H.L.); (J.W.P.); (Y.-H.K.)
| | - Ji Won Park
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (H.L.); (J.W.P.); (Y.-H.K.)
| | - Young-Ho Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (H.L.); (J.W.P.); (Y.-H.K.)
| | - Sunghyouk Park
- College of Pharmacy, Natural Product Research Institute, Seoul National University, Seoul 08826, Korea;
- Correspondence: (S.P.); (J.J.K.); Tel.: +82-(2)-880-7834 (S.P.); +82-(2)-3410-3409 (J.J.K.); Fax: +82-(2)-880-7831 (S.P.); +82-(2)-3410-6983 (J.J.K.)
| | - Jae J. Kim
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea; (H.L.); (J.W.P.); (Y.-H.K.)
- Correspondence: (S.P.); (J.J.K.); Tel.: +82-(2)-880-7834 (S.P.); +82-(2)-3410-3409 (J.J.K.); Fax: +82-(2)-880-7831 (S.P.); +82-(2)-3410-6983 (J.J.K.)
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15
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Li S, Zhang Y, Mu S, Ma M, Liu X, Zhang H. Magnetic organic porous polymer as a solid-phase extraction adsorbent for enrichment and quantitation of gastric cancer biomarkers (P-cresol and 4-hydroxybenzoic acid) in urine samples by UPLC. Mikrochim Acta 2020; 187:388. [PMID: 32542460 DOI: 10.1007/s00604-020-04362-z] [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] [Received: 01/14/2020] [Accepted: 05/31/2020] [Indexed: 01/15/2023]
Abstract
A novel magnetic organic porous polymer (denoted as Fe3O4@PC-POP) was developed for magnetic solid-phase extraction (MSPE) of two gastric cancer biomarkers (P-cresol and 4-hydroxybenzoic acid) from urine samples prior to high-performance liquid chromatographic analysis. The adsorbent was characterized by scanning electron microscope, transmission electron microscope, FTIR, powder X-ray diffraction, and other techniques. The result of dynamic light scattering shows that the particle size of the adsorbent is mainly distributed around 400 nm. Based on the design concept of the Fe3O4@PC-POP, the proposed material can effectively capture the target analytes through electrostatic and hydrophobic interaction mechanism. Furthermore, the enrichment conditions were optimized by the response surface method, and the method was utilized for the determination of P-cresol and 4-hydroxybenzoic acid in real urine samples from health and gastric cancer patients with high enrichment factors (34.8 times for P-cresol and 38.7 times for 4-hydroxybenzoic acid), low limit of detection (0.9-5.0 μg L-1), wide linear ranges (3.0-1000 μg L-1), satisfactory relative standard deviation (2.5%-8.5%), and apparent recoveries (85.3-112% for healthy people's and 86.0-112% for gastric cancer patients' urine samples). This study provides a guided principle for design of the versatile polymer with specific capturing of the target compounds from complex biological samples. Graphical abstract.
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Affiliation(s)
- Shanshan Li
- State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China
| | - Yintang Zhang
- Henan Key Laboratory of Biomolecular Recognition and Sensing, College of Chemistry and Chemical Engineering, Shangqiu Normal University, Shangqiu, 476000, China
| | - Shuai Mu
- State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China
| | - Minrui Ma
- State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China
| | - Xiaoyan Liu
- State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China.
| | - Haixia Zhang
- State Key Laboratory of Applied Organic Chemistry, Key Laboratory of Nonferrous Metals Chemistry and Resources Utilization of Gansu Province and College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, 730000, China
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16
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Dai M, Ma T, Niu Y, Zhang M, Zhu Z, Wang S, Liu H. Analysis of low-molecular-weight metabolites in stomach cancer cells by a simplified and inexpensive GC/MS metabolomics method. Anal Bioanal Chem 2020; 412:2981-2991. [PMID: 32185442 DOI: 10.1007/s00216-020-02543-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2019] [Revised: 02/01/2020] [Accepted: 02/21/2020] [Indexed: 12/26/2022]
Abstract
GC/MS coupled metabolomics analysis, using a simplified and much less expensive silylation process with trimethylsilyl cyanide (TMSCN), was conducted to investigate metabolic abnormalities in stomach cancer cells. Under optimized conditions for derivatization by TMSCN and methanol extraction, 228 metabolites were detected using GC/MS spectrometry analysis, and 89 metabolites were identified using standard compounds and the NIST database. Ten metabolite levels were found to be lower in stomach cancer cells relative to normal cells. Among those ten metabolites, four metabolites-ribose, proline, pyroglutamic acid, and glucose-were known to be linked to cancers. In particular, pyroglutamic acid level showed a drastic reduction of 22-fold in stomach cancer cells. Since glutamine and glutamic acid are known to undergo cyclization to pyroglutamic acid, the 22-fold reduction might be the actual reduction in the levels of glutamine and/or glutamic acid-both known to be cancer-related. Hence, the marked reduction in pyroglutamic acid level might serve as a biomarker to aid early detection of stomach cancer. Graphical abstract.
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Affiliation(s)
- Min Dai
- College of Chemistry, Zhengzhou University, 75 University Road, Zhengzhou, 450052, Henan, China
| | - Ting Ma
- School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, Henan, China
| | - Ying Niu
- College of Chemistry, Zhengzhou University, 75 University Road, Zhengzhou, 450052, Henan, China
| | - Mengmeng Zhang
- College of Chemistry, Zhengzhou University, 75 University Road, Zhengzhou, 450052, Henan, China
| | - Zhiwu Zhu
- College of Chemistry, Zhengzhou University, 75 University Road, Zhengzhou, 450052, Henan, China
| | - Shaomin Wang
- College of Chemistry, Zhengzhou University, 75 University Road, Zhengzhou, 450052, Henan, China.
| | - Hongmin Liu
- School of Pharmaceutical Sciences, Zhengzhou University, 100 Science Avenue, Zhengzhou, 450001, Henan, China
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17
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Dinges SS, Hohm A, Vandergrift LA, Nowak J, Habbel P, Kaltashov IA, Cheng LL. Cancer metabolomic markers in urine: evidence, techniques and recommendations. Nat Rev Urol 2020; 16:339-362. [PMID: 31092915 DOI: 10.1038/s41585-019-0185-3] [Citation(s) in RCA: 108] [Impact Index Per Article: 21.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Urinary tests have been used as noninvasive, cost-effective tools for screening, diagnosis and monitoring of diseases since ancient times. As we progress through the 21st century, modern analytical platforms have enabled effective measurement of metabolites, with promising results for both a deeper understanding of cancer pathophysiology and, ultimately, clinical translation. The first study to measure metabolomic urinary cancer biomarkers using NMR and mass spectrometry (MS) was published in 2006 and, since then, these techniques have been used to detect cancers of the urological system (kidney, prostate and bladder) and nonurological tumours including those of the breast, ovary, lung, liver, gastrointestinal tract, pancreas, bone and blood. This growing field warrants an assessment of the current status of research developments and recommendations to help systematize future research.
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Affiliation(s)
- Sarah S Dinges
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Haematology and Oncology, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Annika Hohm
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Diagnostic and Interventional Neuroradiology, University Hospital of Würzburg, Würzburg, Germany
| | - Lindsey A Vandergrift
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Johannes Nowak
- Department of Diagnostic and Interventional Radiology, University Hospital of Würzburg, Würzburg, Germany
| | - Piet Habbel
- Department of Haematology and Oncology, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Igor A Kaltashov
- Department of Chemistry, University of Massachusetts-Amherst, Amherst, MA, USA.
| | - Leo L Cheng
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. .,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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18
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Review and Comparison of Cancer Biomarker Trends in Urine as a Basis for New Diagnostic Pathways. Cancers (Basel) 2019; 11:cancers11091244. [PMID: 31450698 PMCID: PMC6770126 DOI: 10.3390/cancers11091244] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 08/20/2019] [Accepted: 08/22/2019] [Indexed: 12/24/2022] Open
Abstract
Cancer is one of the major causes of mortality worldwide and its already large burden is projected to increase significantly in the near future with a predicted 22 million new cancer cases and 13 million cancer-related deaths occurring annually by 2030. Unfortunately, current procedures for diagnosis are characterized by low diagnostic accuracies. Given the proved correlation between cancer presence and alterations of biological fluid composition, many researchers suggested their characterization to improve cancer detection at early stages. This paper reviews the information that can be found in the scientific literature, regarding the correlation of different cancer forms with the presence of specific metabolites in human urine, in a schematic and easily interpretable form, because of the huge amount of relevant literature. The originality of this paper relies on the attempt to point out the odor properties of such metabolites, and thus to highlight the correlation between urine odor alterations and cancer presence, which is proven by recent literature suggesting the analysis of urine odor for diagnostic purposes. This investigation aims to evaluate the possibility to compare the results of studies based on different approaches to be able in the future to identify those compounds responsible for urine odor alteration.
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19
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Chen Y, Zhang J, Guo L, Liu L, Wen J, Xu L, Yan M, Li Z, Zhang X, Nan P, Jiang J, Ji J, Zhang J, Cai W, Zhuang H, Wang Y, Zhu Z, Yu Y. A characteristic biosignature for discrimination of gastric cancer from healthy population by high throughput GC-MS analysis. Oncotarget 2018; 7:87496-87510. [PMID: 27589838 PMCID: PMC5350005 DOI: 10.18632/oncotarget.11754] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2016] [Accepted: 07/19/2016] [Indexed: 12/17/2022] Open
Abstract
Early diagnosis of gastric cancer is crucial to improve patient′ outcome. A good biomarker will function in early diagnosis for gastric cancer. In order to find practical and cost-effective biomarkers, we used gas chromatography combined mass spectrometer (GC-MS) to profile urinary metabolites on 293 urine samples. Ninety-four samples are taken as training set, others for validating study. Orthogonal partial least squares discriminant analysis (OPLS-DA), significance analysis of microarray (SAM) and Mann-Whitney U test are used for data analysis. The diagnostic value of urinary metabolites was evaluated by ROC curve. As results, Seventeen metabolites are significantly different between patients and healthy controls in training set. Among them, 14 metabolites show diagnostic value better than classic blood biomarkers by quantitative assay on validation set. Ten of them are amino acids and four are organic metabolites. Importantly, proline, p-cresol and 4-hydroxybenzoic acid disclose outcome-prediction value by means of survival analysis. Therefore, the examination of urinary metabolites is a promising noninvasive strategy for gastric cancer screening.
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Affiliation(s)
- Yinan Chen
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Zhang
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lei Guo
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lei Liu
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jingran Wen
- Tongji University, School of Life Science and Technology, Shanghai, China
| | - Lu Xu
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Yan
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zuofeng Li
- Tongji University, School of Life Science and Technology, Shanghai, China
| | - Xiaoyan Zhang
- Tongji University, School of Life Science and Technology, Shanghai, China
| | - Peng Nan
- School of Life Sciences, Fudan University, Shanghai, China
| | - Jinling Jiang
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jun Ji
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jianian Zhang
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wei Cai
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huisheng Zhuang
- School of Environmental Science and Engineering, Shanghai Jiao Tong University, Shanghai, China
| | - Yan Wang
- College of Public Health, Shanghai Jiao Tong University, School of Medicine, Shanghai, China
| | - Zhenggang Zhu
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yingyan Yu
- Department of Surgery of Ruijin Hospital, and Shanghai Institute of Digestive Surgery, Shanghai Key Laboratory for Gastric Neoplasms, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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20
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Recent advances in the applications of metabolomics in eye research. Anal Chim Acta 2018; 1037:28-40. [PMID: 30292303 DOI: 10.1016/j.aca.2018.01.060] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Revised: 01/26/2018] [Accepted: 01/29/2018] [Indexed: 11/21/2022]
Abstract
Metabolomics, the identification and quantitation of metabolites in a system, have been applied to identify new biomarkers or elucidate disease mechanism. In this review, we discussed the application of metabolomics in several ocular diseases and recent developments in metabolomics regarding tear fluids analysis, data acquisition and processing.
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21
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Phillips TM. Recent advances in CE and microchip-CE in clinical applications: 2014 to mid-2017. Electrophoresis 2017; 39:126-135. [PMID: 28853177 DOI: 10.1002/elps.201700283] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2017] [Revised: 08/09/2017] [Accepted: 08/10/2017] [Indexed: 11/11/2022]
Abstract
CE and microchip CE (ME) are powerful tools for the analysis of a number of different analytes and have been applied to a variety of clinical fields and human samples. This review will present an overview of the most recent applications of these techniques to different areas of clinical medicine during the period of 2014 to mid-2017. CE and ME have been applied to clinical chemistry, drug detection and monitoring, hematology, infectious diseases, oncology, endocrinology, neonatology, nephrology, and genetic screening. Samples examined range from serum, plasma, and urine to lest utilized materials such as tears, cerebral spinal fluid, sweat, saliva, condensed breath, single cells, and biopsy tissue. Examples of clinical applications will be given along with the various detection systems employed.
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Affiliation(s)
- Terry M Phillips
- Department of Pharmaceutics, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA
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22
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Armitage EG, Ciborowski M. Applications of Metabolomics in Cancer Studies. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 965:209-234. [PMID: 28132182 DOI: 10.1007/978-3-319-47656-8_9] [Citation(s) in RCA: 59] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Since the start of metabolomics as a field of research, the number of studies related to cancer has grown to such an extent that cancer metabolomics now represents its own discipline. In this chapter, the applications of metabolomics in cancer studies are explored. Different approaches and analytical platforms can be employed for the analysis of samples depending on the goal of the study and the aspects of the cancer metabolome being investigated. Analyses have concerned a range of cancers including lung, colorectal, bladder, breast, gastric, oesophageal and thyroid, amongst others. Developments in these strategies and methodologies that have been applied are discussed, in addition to exemplifying the use of cancer metabolomics in the discovery of biomarkers and in the assessment of therapy (both pharmaceutical and nutraceutical). Finally, the application of cancer metabolomics in personalised medicine is presented.
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Affiliation(s)
- Emily Grace Armitage
- Centre for Metabolomics and Bioanalysis (CEMBIO), Faculty of Pharmacy, Universidad CEU San Pablo, Campus Monteprincipe, Madrid, Spain. .,Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical Veterinary and Life Sciences, Sir Graeme Davies Building, University of Glasgow, Glasgow, UK. .,Glasgow Polyomics, Wolfson Wohl Cancer Research Centre, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
| | - Michal Ciborowski
- Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland
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Rodrigues KT, Cieslarová Z, Tavares MFM, Simionato AVC. Strategies Involving Mass Spectrometry Combined with Capillary Electrophoresis in Metabolomics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 965:99-141. [DOI: 10.1007/978-3-319-47656-8_5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Capillary electrophoresis mass spectrometry as a tool for untargeted metabolomics. Bioanalysis 2017; 9:99-130. [PMID: 27921456 DOI: 10.4155/bio-2016-0216] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Highly polar and ionic metabolites, such as sugars, most amino acids, organic acids or nucleotides are not retained by conventional reversed-phase LC columns and polar stationary phases and hydrophilic-interaction LC lacks of robustness, which is still limiting their applications for untargeted metabolomics where reproducibility is a must. Biological samples such as blood, urine or even tissues include many hydrophilic compounds secreted from cells, their analysis is essential for biomarker discovery, disease progression or treatment effects. This review focuses on CE coupled to MS as a mature technique for untargeted metabolomics including sample pretreatment, types of matrices, analytical methods, applications and data treatment strategies for polar compound analysis in biological matrices. The main applications and results of CE-MS in untargeted metabolomics are discussed and presented in a tabulated format.
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Sarosiek I, Schicho R, Blandon P, Bashashati M. Urinary metabolites as noninvasive biomarkers of gastrointestinal diseases: A clinical review. World J Gastrointest Oncol 2016; 8:459-465. [PMID: 27190585 PMCID: PMC4865713 DOI: 10.4251/wjgo.v8.i5.459] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2015] [Revised: 01/12/2016] [Accepted: 03/09/2016] [Indexed: 02/05/2023] Open
Abstract
The diagnosis of gastrointestinal (GI) disorders is usually based on invasive techniques such as endoscopy. A key important factor in GI cancer is early diagnosis which warrants development of non- or less-invasive diagnostic techniques. In addition, monitoring and surveillance are other important parts in the management of GI diseases. Metabolomics studies with nuclear magnetic resonance and mass spectrometry can measure the concentration of more than 3000 chemical compounds in the urine providing possible chemical signature in different diseases and during health. In this review, we discuss the urinary metabolomics signature of different GI diseases including GI cancer and elaborate on how these biomarkers could be used for the classification, early diagnosis and the monitoring of the patients. Moreover, we discuss future directions of this still evolving field of research.
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Coghlin C, Murray GI. Progress in the development of protein biomarkers of oesophageal and gastric cancers. Proteomics Clin Appl 2016; 10:532-545. [PMID: 26582241 DOI: 10.1002/prca.201500079] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2015] [Revised: 10/10/2015] [Accepted: 11/12/2015] [Indexed: 01/03/2025]
Abstract
Upper gastrointestinal cancers originating in the oesophagus and stomach often present late and have a very poor prognosis. Treatment options include surgery for localised disease but, increasingly, neoadjuvant chemotherapy and radiotherapy are being employed to improve outcome. There is often a variable response to neoadjuvant treatment between individual patients and side effects are relatively common. There is an urgent need for novel biomarkers of upper gastrointestinal cancer, not only to improve screening and early diagnosis of the oesophageal and gastric cancers when treatment options are potentially more effective, but also to accurately guide therapy in more advanced disease. The development of predictive biomarkers will also help to more effectively identify those patients that will benefit from targeted therapies. Although many promising results have been derived from these studies there remains a lack of validated clinically applicable biomarkers available for translation into routine clinical use. This review will provide an overview of the recent proteomic research on upper gastrointestinal cancer protein biomarker identification and validation. The challenges faced in the development of validated, clinically acceptable and accurate protein biomarkers will also be discussed, along with possible areas of future progress.
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Affiliation(s)
- Caroline Coghlin
- Department of Cellular Pathology, Craigavon Area Hospital, Portadown, UK
| | - Graeme I Murray
- Pathology, Division of Applied Medicine, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
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Yang FX, Wang YX, Lu YH, Yang DZ, Tang DQ, Fan XL. Metabolic analysis and mechanism of lipids, amino acids and carbohydrates in gastrointestinal cancer. Shijie Huaren Xiaohua Zazhi 2016; 24:722-730. [DOI: 10.11569/wcjd.v24.i5.722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Metabolomics has recently been applied in a variety of biomedical research fields. However, there have been no articles on the application of metabonomics in gastrointestinal cancer and the relevant detailed mechanisms. In this article, the application of metabolomics in early diagnosis of gastrointestinal cancer is reviewed, and the metabolic role and metabolic mechanism of lipids, amino acids and carbohydrates, as well as the future challenge of metabolomics in the clinical application are summarized.
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Yuan LW, Yamashita H, Seto Y. Glucose metabolism in gastric cancer: The cutting-edge. World J Gastroenterol 2016; 22:2046-2059. [PMID: 26877609 PMCID: PMC4726677 DOI: 10.3748/wjg.v22.i6.2046] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2015] [Revised: 09/18/2015] [Accepted: 12/01/2015] [Indexed: 02/06/2023] Open
Abstract
Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer.
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Nishiumi S, Suzuki M, Kobayashi T, Matsubara A, Azuma T, Yoshida M. Metabolomics for biomarker discovery in gastroenterological cancer. Metabolites 2014; 4:547-71. [PMID: 25003943 PMCID: PMC4192679 DOI: 10.3390/metabo4030547] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2014] [Revised: 06/11/2014] [Accepted: 06/25/2014] [Indexed: 12/15/2022] Open
Abstract
The study of the omics cascade, which involves comprehensive investigations based on genomics, transcriptomics, proteomics, metabolomics, etc., has developed rapidly and now plays an important role in life science research. Among such analyses, metabolome analysis, in which the concentrations of low molecular weight metabolites are comprehensively analyzed, has rapidly developed along with improvements in analytical technology, and hence, has been applied to a variety of research fields including the clinical, cell biology, and plant/food science fields. The metabolome represents the endpoint of the omics cascade and is also the closest point in the cascade to the phenotype. Moreover, it is affected by variations in not only the expression but also the enzymatic activity of several proteins. Therefore, metabolome analysis can be a useful approach for finding effective diagnostic markers and examining unknown pathological conditions. The number of studies involving metabolome analysis has recently been increasing year-on-year. Here, we describe the findings of studies that used metabolome analysis to attempt to discover biomarker candidates for gastroenterological cancer and discuss metabolome analysis-based disease diagnosis.
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Affiliation(s)
- Shin Nishiumi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
| | - Makoto Suzuki
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
| | - Atsuki Matsubara
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
| | - Takeshi Azuma
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
| | - Masaru Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chu-o-ku, Kobe, Hyogo 650-0017, Japan.
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Metabolomic profiling of neoplastic lesions in mice. Methods Enzymol 2014. [PMID: 24924137 DOI: 10.1016/b978-0-12-801329-8.00013-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023]
Abstract
Most cancers develop upon the accumulation of genetic alterations that provoke and sustain the transformed phenotype. Several metabolomic approaches now allow for the global assessment of intermediate metabolites, generating profound insights into the metabolic rewiring associated with malignant transformation. The metabolomic profiling of neoplastic lesions growing in mice, irrespective of their origin, can provide invaluable information on the mechanisms underlying oncogenesis, tumor progression, and response to therapy. Moreover, the metabolomic profiling of tumors growing in mice may result in the identification of novel diagnostic or prognostic biomarkers, which is of great clinical significance. Several methods can be applied to the metabolomic profiling of neoplastic lesions in mice, including mass spectrometry-based techniques (e.g., gas chromatography-, capillary electrophoresis-, or liquid chromatography-coupled mass spectrometry) as well as nuclear magnetic resonance. Here, we compare and discuss the advantages and disadvantages of all these techniques to provide a concise and reliable guide for readers interested in this active area of investigation.
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