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McDonnell D, Afolabi PR, Niazi U, Wilding S, Griffiths GO, Swann JR, Byrne CD, Hamady ZZ. Metabolite Changes Associated with Resectable Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2025; 17:1150. [PMID: 40227642 DOI: 10.3390/cancers17071150] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2025] [Revised: 03/24/2025] [Accepted: 03/28/2025] [Indexed: 04/15/2025] Open
Abstract
INTRODUCTION Pancreatic ductal adenocarcinoma (PDAC) is insidious, with only 15-20% of those diagnosed suitable for surgical resection as it is either too advanced and has invaded local structures or has already spread to distant sites. The associated tumor microenvironment provides a protective shield which limits the efficacy of chemotherapeutic agents, but also impairs the delivery of nutrients required for the PDAC cells. To compensate for this, metabolic adaptions occur to provide alternative sources of fuel. The aim of this study is to explore metabolomic differences between participants with resectable PDAC compared to healthy volunteers (HV). The objectives were to use nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to determine if resectable PDAC induces sufficient metabolic adaptations and variations which could be used to discriminate between the two groups. METHODS Plasma samples were collected from fasted individuals with resectable PDAC (n = 23, median age 68 [IQR 56-75], 69.6% male) and HV (n = 24, median age 63 [IQR 58-71], 54.2% male). Samples were analyzed using NMR and the Biocrates MxP Quant 500 kit at University Hospital Southampton. RESULTS NMR spectroscopy identified six independent metabolites that significantly discriminated between the PDAC and HV groups, including elevated plasma concentrations of 3-hydroxybutyrate and citrate, with decreased amounts of glutamine and histidine. MS analysis identified 84 metabolites with a significant difference between the PDAC and HV cohorts. The metabolites with a fold change (FC) > 1.5 in the PDAC population were conjugated bile acids (taurocholic acid, glycocholic acid, and glycochenodexoycholic acid). DISCUSSION In conclusion, using metabolomics, biochemical differences between resectable PDAC and HV were detected. These differences indicate metabolic plasticity and utilization of alternative fuel sources.
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Affiliation(s)
- Declan McDonnell
- Human Development & Health, University of Southampton, Southampton SO16 6YD, UK
- Department of General Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK
| | - Paul R Afolabi
- Human Development & Health, University of Southampton, Southampton SO16 6YD, UK
| | - Umar Niazi
- Human Development & Health, University of Southampton, Southampton SO16 6YD, UK
| | - Sam Wilding
- Cancer Research UK Southampton Clinical Trials Unit, University of Southampton, Southampton SO16 6YD, UK
| | - Gareth O Griffiths
- Department of General Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK
- Cancer Research UK Southampton Clinical Trials Unit, University of Southampton, Southampton SO16 6YD, UK
| | - Jonathan R Swann
- Human Development & Health, University of Southampton, Southampton SO16 6YD, UK
| | - Christopher D Byrne
- Human Development & Health, University of Southampton, Southampton SO16 6YD, UK
- Department of General Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK
| | - Zaed Z Hamady
- Human Development & Health, University of Southampton, Southampton SO16 6YD, UK
- Department of General Surgery, University Hospital Southampton NHS Foundation Trust, Southampton SO16 6YD, UK
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Maiti A, Mondal S, Choudhury S, Bandopadhyay A, Mukherjee S, Sikdar N. Oncometabolites in pancreatic cancer: Strategies and its implications. World J Exp Med 2024; 14:96005. [PMID: 39713078 PMCID: PMC11551704 DOI: 10.5493/wjem.v14.i4.96005] [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] [Received: 04/24/2024] [Revised: 08/24/2024] [Accepted: 09/14/2024] [Indexed: 10/31/2024] Open
Abstract
Pancreatic cancer (PanCa) is a catastrophic disease, being third lethal in both the genders around the globe. The possible reasons are extreme disease invasiveness, highly fibrotic and desmoplastic stroma, dearth of confirmatory diagnostic approaches and resistance to chemotherapeutics. This inimitable tumor microenvironment (TME) or desmoplasia with excessive extracellular matrix accumulation, create an extremely hypovascular, hypoxic and nutrient-deficient zone inside the tumor. To survive, grow and proliferate in such tough TME, pancreatic tumor and stromal cells transform their metabolism. Transformed glucose, glutamine, fat, nucleotide metabolism and inter-metabolite communication between tumor and TME in synergism, impart therapy resistance, and immunosuppression in PanCa. Thus, a finer knowledge of altered metabolism would uncover its metabolic susceptibilities. These unique metabolic targets may help to device novel diagnostic/prognostic markers and therapeutic strategies for better management of PanCa. In this review, we sum up reshaped metabolic pathways in PanCa to formulate detection and remedial strategies of this devastating disease.
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Affiliation(s)
- Arunima Maiti
- Suraksha Diagnostics Pvt Ltd, Newtown, Rajarhat, Kolkata 700156, West Bengal, India
| | - Susmita Mondal
- Department of Zoology, Diamond Harbour Women’s University, Diamond Harbour 743368, West Bengal, India
| | - Sounetra Choudhury
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, West Bengal, India
| | | | - Sanghamitra Mukherjee
- Department of Pathology, RG Kar Medical College and Hospital, Kolkata 700004, West Bengal, India
| | - Nilabja Sikdar
- Human Genetics Unit, Indian Statistical Institute, Kolkata 700108, West Bengal, India
- Scientist G, Estuarine and Coastal Studies Foundation, Howrah 711101, West Bengal, India
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López-López Á, López-Gonzálvez Á, Barbas C. Metabolomics for searching validated biomarkers in cancer studies: a decade in review. Expert Rev Mol Diagn 2024; 24:601-626. [PMID: 38904089 DOI: 10.1080/14737159.2024.2368603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 06/12/2024] [Indexed: 06/22/2024]
Abstract
INTRODUCTION In the dynamic landscape of modern healthcare, the ability to anticipate and diagnose diseases, particularly in cases where early treatment significantly impacts outcomes, is paramount. Cancer, a complex and heterogeneous disease, underscores the critical importance of early diagnosis for patient survival. The integration of metabolomics information has emerged as a crucial tool, complementing the genotype-phenotype landscape and providing insights into active metabolic mechanisms and disease-induced dysregulated pathways. AREAS COVERED This review explores a decade of developments in the search for biomarkers validated within the realm of cancer studies. By critically assessing a diverse array of research articles, clinical trials, and studies, this review aims to present an overview of the methodologies employed and the progress achieved in identifying and validating biomarkers in metabolomics results for various cancer types. EXPERT OPINION Through an exploration of more than 800 studies, this review has allowed to establish a general idea about state-of-art in the search of biomarkers in metabolomics studies involving cancer which include certain level of results validation. The potential for metabolites as diagnostic markers to reach the clinic and make a real difference in patient health is substantial, but challenges remain to be explored.
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Affiliation(s)
- Ángeles López-López
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Madrid, Spain
| | - Ángeles López-Gonzálvez
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Madrid, Spain
| | - Coral Barbas
- Centro de Metabolómica y Bioanálisis (CEMBIO), Facultad de Farmacia, Universidad San Pablo-CEU, CEU Universities, Boadilla del Monte, Madrid, Spain
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Ma X, Fernández FM. Advances in mass spectrometry imaging for spatial cancer metabolomics. MASS SPECTROMETRY REVIEWS 2024; 43:235-268. [PMID: 36065601 PMCID: PMC9986357 DOI: 10.1002/mas.21804] [Citation(s) in RCA: 53] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Revised: 08/02/2022] [Accepted: 08/02/2022] [Indexed: 05/09/2023]
Abstract
Mass spectrometry (MS) has become a central technique in cancer research. The ability to analyze various types of biomolecules in complex biological matrices makes it well suited for understanding biochemical alterations associated with disease progression. Different biological samples, including serum, urine, saliva, and tissues have been successfully analyzed using mass spectrometry. In particular, spatial metabolomics using MS imaging (MSI) allows the direct visualization of metabolite distributions in tissues, thus enabling in-depth understanding of cancer-associated biochemical changes within specific structures. In recent years, MSI studies have been increasingly used to uncover metabolic reprogramming associated with cancer development, enabling the discovery of key biomarkers with potential for cancer diagnostics. In this review, we aim to cover the basic principles of MSI experiments for the nonspecialists, including fundamentals, the sample preparation process, the evolution of the mass spectrometry techniques used, and data analysis strategies. We also review MSI advances associated with cancer research in the last 5 years, including spatial lipidomics and glycomics, the adoption of three-dimensional and multimodal imaging MSI approaches, and the implementation of artificial intelligence/machine learning in MSI-based cancer studies. The adoption of MSI in clinical research and for single-cell metabolomics is also discussed. Spatially resolved studies on other small molecule metabolites such as amino acids, polyamines, and nucleotides/nucleosides will not be discussed in the context.
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Affiliation(s)
- Xin Ma
- School of Chemistry and Biochemistry and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
| | - Facundo M Fernández
- School of Chemistry and Biochemistry and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, Georgia, USA
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Wahab MRA, Palaniyandi T, Ravi M, Viswanathan S, Baskar G, Surendran H, Gangadharan SGD, Rajendran BK. Biomarkers and biosensors for early cancer diagnosis, monitoring and prognosis. Pathol Res Pract 2023; 250:154812. [PMID: 37741139 DOI: 10.1016/j.prp.2023.154812] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2023] [Revised: 08/22/2023] [Accepted: 09/08/2023] [Indexed: 09/25/2023]
Abstract
Cancers continue to be of major concern due to their serious global socioeconomic impact, apart from the continued increase in the incidence of various cancer types. A major challenge that this disease poses is due to the low "early detection" rates which limit the therapeutic outcomes for the affected individuals. Current research has highlighted the discovering biomarkers that help in early cancer detection and the development of technologies for the detection and quantification of such biomarkers. Biomarkers range from proteins to nucleic acids, and can be specific to a particular cancer type. Detection and quantification of such biomarkers at low levels from biological samples is being made possible by the advent of developing biosensors and by using biomedical engineering technologies such as tumor-on-a-chip models. Here, we present biomarkers that can be helpful for the early detection of breast, colorectal, esophageal, lung, liver, ovarian, and prostate cancer. In addition, we discuss the potential of circulating tumor cell DNA (ctDNA) as an early diagnostic marker. Finally, biosensors available for the detection of cancer biomarkers, which is a recent advancement in this area of research, are discussed.
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Affiliation(s)
| | - Thirunavukkarasu Palaniyandi
- Department of Biotechnology, Dr. M.G.R Educational and Research Institute, Chennai 600095; Department of Anatomy, Biomedical Research Unit and Laboratory Animal Centre, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Science, Saveetha University, Chennai, Tamil Nadu, India.
| | - Maddaly Ravi
- Department of Human Genetics, Sri Ramachandra Institute of Higher Education and Research, Chennai 600116, Tamil Nadu, India
| | - Sandhiya Viswanathan
- Department of Biotechnology, Dr. M.G.R Educational and Research Institute, Chennai 600095
| | - Gomathy Baskar
- Department of Biotechnology, Dr. M.G.R Educational and Research Institute, Chennai 600095
| | - Hemapreethi Surendran
- Department of Biotechnology, Dr. M.G.R Educational and Research Institute, Chennai 600095
| | - S G D Gangadharan
- Department of Medical Oncology, Madras Medical College, R. G. G. G. H., Chennai, Tamil Nadu, India
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Amer B, Deshpande RR, Bird SS. Simultaneous Quantitation and Discovery (SQUAD) Analysis: Combining the Best of Targeted and Untargeted Mass Spectrometry-Based Metabolomics. Metabolites 2023; 13:metabo13050648. [PMID: 37233689 DOI: 10.3390/metabo13050648] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 04/27/2023] [Accepted: 05/05/2023] [Indexed: 05/27/2023] Open
Abstract
Untargeted and targeted approaches are the traditional metabolomics workflows acquired for a wider understanding of the metabolome under focus. Both approaches have their strengths and weaknesses. The untargeted, for example, is maximizing the detection and accurate identification of thousands of metabolites, while the targeted is maximizing the linear dynamic range and quantification sensitivity. These workflows, however, are acquired separately, so researchers compromise either a low-accuracy overview of total molecular changes (i.e., untargeted analysis) or a detailed yet blinkered snapshot of a selected group of metabolites (i.e., targeted analysis) by selecting one of the workflows over the other. In this review, we present a novel single injection simultaneous quantitation and discovery (SQUAD) metabolomics that combines targeted and untargeted workflows. It is used to identify and accurately quantify a targeted set of metabolites. It also allows data retro-mining to look for global metabolic changes that were not part of the original focus. This offers a way to strike the balance between targeted and untargeted approaches in one single experiment and address the two approaches' limitations. This simultaneous acquisition of hypothesis-led and discovery-led datasets allows scientists to gain more knowledge about biological systems in a single experiment.
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Affiliation(s)
- Bashar Amer
- Thermo Fisher Scientific, San Jose, 95134 CA, USA
| | | | - Susan S Bird
- Thermo Fisher Scientific, San Jose, 95134 CA, USA
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Pelling M, Chandrapalan S, West E, Arasaradnam RP. A Systematic Review and Meta-Analysis: Volatile Organic Compound Analysis in the Detection of Hepatobiliary and Pancreatic Cancers. Cancers (Basel) 2023; 15:2308. [PMID: 37190235 PMCID: PMC10136496 DOI: 10.3390/cancers15082308] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/29/2023] [Accepted: 04/04/2023] [Indexed: 05/17/2023] Open
Abstract
BACKGROUND Hepatobiliary cancers are notoriously difficult to detect, frequently leading to diagnosis in later stages of disease when curative treatment is not an option. The currently used biomarkers such as AFP (alpha-fetoprotein) and CA19.9 lack sensitivity and specificity. Hence, there is an unmet need for an alternative biomarker. AIM To evaluate the diagnostic accuracy of volatile organic compounds (VOCs) for the detection of hepatobiliary and pancreatic cancers. METHODS A systematic review of VOCs' use in the detection of hepatobiliary and pancreatic cancers was performed. A meta-analysis was performed using the software R. Heterogeneity was explored through meta-regression analysis. RESULTS A total of 18 studies looking at 2296 patients were evaluated. Pooled sensitivity and specificity of VOCs for the detection of hepatobiliary and pancreatic cancer were 0.79 (95% CI, 0.72-0.85) and 0.81 (97.5% CI, 0.76-0.85), respectively. The area under the curve was 0.86. Meta-regression analysis showed that the sample media used contributed to heterogeneity. Bile-based VOCs showed the highest precision values, although urine and breath are preferred for their feasibility. CONCLUSIONS Volatile organic compounds have the potential to be used as an adjunct tool to aid in the early diagnosis of hepatobiliary cancers.
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Affiliation(s)
- Melina Pelling
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | | | - Emily West
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
| | - Ramesh P. Arasaradnam
- Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK
- Department of Gastroenterology, University Hospital of Coventry and Warwickshire, Coventry CV2 2DX, UK
- Health, Biological & Experimental Sciences, University of Coventry, Coventry CV1 5FB, UK
- School of Health Sciences, University of Leicester, Leicester LE1 7RH, UK
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Michálková L, Horník Š, Sýkora J, Setnička V, Bunganič B. Prediction of Pathologic Change Development in the Pancreas Associated with Diabetes Mellitus Assessed by NMR Metabolomics. J Proteome Res 2023. [PMID: 37018516 DOI: 10.1021/acs.jproteome.3c00047] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/07/2023]
Abstract
Nuclear magnetic resonance (NMR) metabolomics was used for identification of metabolic changes in pancreatic cancer (PC) blood plasma samples when compared to healthy controls or diabetes mellitus patients. An increased number of PC samples enabled a subdivision of the group according to individual PC stages and the construction of predictive models for finer classification of at-risk individuals recruited from patients with recently diagnosed diabetes mellitus. High-performance values of orthogonal partial least squares (OPLS) discriminant analysis were found for discrimination between individual PC stages and both control groups. The discrimination between early and metastatic stages was achieved with only 71.5% accuracy. A predictive model based on discriminant analyses between individual PC stages and the diabetes mellitus group identified 12 individuals out of 59 as at-risk of development of pathological changes in the pancreas, and four of them were classified as at moderate risk.
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Affiliation(s)
- Lenka Michálková
- Institute of Chemical Process Fundamentals of the CAS, 165 00 Prague 6, Czech Republic
- Department of Analytical Chemistry, University of Chemistry and Technology, Prague, 166 28 Prague 6, Czech Republic
| | - Štěpán Horník
- Institute of Chemical Process Fundamentals of the CAS, 165 00 Prague 6, Czech Republic
| | - Jan Sýkora
- Laboratory of NMR Spectroscopy, University of Chemistry and Technology, Prague, 166 28 Prague 6, Czech Republic
| | - Vladimír Setnička
- Department of Analytical Chemistry, University of Chemistry and Technology, Prague, 166 28 Prague 6, Czech Republic
| | - Bohuš Bunganič
- Department of Internal Medicine, 1st Faculty of Medicine of Charles University and Military University Hospital, 169 02 Prague 6, Czech Republic
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Zhao R, Ren S, Li C, Guo K, Lu Z, Tian L, He J, Zhang K, Cao Y, Liu S, Li D, Wang Z. Biomarkers for pancreatic cancer based on tissue and serum metabolomics analysis in a multicenter study. Cancer Med 2023; 12:5158-5171. [PMID: 36161527 PMCID: PMC9972159 DOI: 10.1002/cam4.5296] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2022] [Revised: 08/10/2022] [Accepted: 09/15/2022] [Indexed: 11/08/2022] Open
Abstract
BACKGROUND Early detection of pancreatic ductal adenocarcinoma (PDAC) may improve the prognosis of patients. This study was to identify metabolic features of PDAC and to discover early detection biomarkers for PDAC by tissue and serum metabolomics analysis. METHODS We conducted nontargeted metabolomics analysis in tissue samples of 51 PDAC tumors, 40 noncancerous pancreatic tissues (NT), and 14 benign pancreatic neoplasms (BP) as well as serum samples from 80 patients with PDAC, 36 with BP, and 48 healthy controls (Ctr). The candidate metabolites identified from the initial analysis were further quantified using targeted analysis in serum samples of an independent cohort of 22 early stage PDAC, 27 BP, and 27 Ctr subjects. Unconditional binary logistic regression analysis was used to construct the optimal model for PDAC diagnosis. RESULTS Upregulated levels of fatty acids and lipids and downregulated amino acids were observed in tissue and serum samples of PDAC patients. Proline, creatine, and palmitic acid were identified as a panel of potential biomarkers to distinguish PDAC from BP and Ctr (odds ratio = 2.17, [95% confidence interval 1.34-3.53]). The three markers showed area under the receiver-operating characteristic curves (AUCs) of 0.854 and 0.865, respectively, for the comparison of PDAC versus Ctr and PDAC versus BP. The AUCs were 0.830 and 0.852 in the validation set and were improved to 0.949 and 0.909 when serum carbohydrate antigen 19-9 (CA19-9) was added to the model. CONCLUSION The novel metabolite biomarker panel identified in this study exhibited promising performance in distinguishing PDAC from BP or Ctr, especially in combination with CA19-9.
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Affiliation(s)
- Rui Zhao
- Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Shuai Ren
- Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Changyin Li
- Department of Clinical Pharmacology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Kai Guo
- Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Zipeng Lu
- Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Lei Tian
- Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Jian He
- Department of Nuclear Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China
| | - Kai Zhang
- Pancreas Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China
| | - Yingying Cao
- Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Shijia Liu
- Department of Pharmacy, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Donghui Li
- Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
| | - Zhongqiu Wang
- Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
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Fang N, Zhang C, Hu H, Li Y, Wang X, Zhao X, Jiang J. Histology and metabonomics reveal the toxic effects of kresoxim-methyl on adult zebrafish. CHEMOSPHERE 2022; 309:136739. [PMID: 36223820 DOI: 10.1016/j.chemosphere.2022.136739] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 09/28/2022] [Accepted: 10/01/2022] [Indexed: 06/16/2023]
Abstract
Studies have shown that kresoxim-methyl (KM) and other strobilurin fungicides have toxic effects on aquatic organisms. However, the potential deleterious effects of kresoxim-methyl (KM) on adult zebrafish regarding the ecological risk of environmental concentration remain unclear. Here, the histology and untargeted metabonomics was used to investigate the adverse effect on female zebrafish after exposure to KM at environmental concentration, aquatic life benchmark and one-half LC50 of adult zebrafish. Results demonstrated KM affected zebrafish liver, ovary and intestine development, blurred the boundary between hepatocytes or caused hepatic vacuoles, increased the percentage of perinucleolar oocyte and cortical alveolus oocyte, decreased intestinal goblet cells and disturbed villus and wall integrity after 21 d exposure. Metabonomics showed different concentrations of KM simultaneously influenced the metabolites annotated to vitamin digestion and absorption, serotonergic synapse, retinol metabolism, ovarian steroidogenesis and arachidonic acid (AA) metabolism in zebrafish liver. Results showed the decreased triglyceride and cholesterol levels, as well as the metabolic alterations in amino acid, lipid, vitamin and retinol metabolism caused by KM, might disturb the energy supply for normal liver development and oocyte maturation. In addition, KM altered the transcription of Tdo2a, Tdo2b, Ido1, Cxcl8b, Cyp7a, Cyp11a, Cyp11b, Cyp17a, Cyp19a, Hsd3β, Hsd17β, Pla2, Ptgs2a and Ptgs2b, the level of TG, TC, MDA, IFN, IL6 and Ca2+, and the activity of CAT, SOD Ca2+-ATPase in zebrafish liver. Moreover, cytoscape analysis suggested the disturbed AA metabolism caused by KM, might interconnect multiple metabolic pathways to share implicated function in the regulation of oocyte maturation and immune response. Current study brought us closer to an incremental understanding of the toxic mechanism of KM on adult zebrafish, indicated there was crosstalk among different regulatory pathways to regulate the metabolic disorders and biologically hazardous effects induced by KM.
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Affiliation(s)
- Nan Fang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China
| | - Changpeng Zhang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China
| | - Haoze Hu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China; College of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315832, Zhejiang, China
| | - Yanjie Li
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China
| | - Xiangyun Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China
| | - Xueping Zhao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China
| | - Jinhua Jiang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory for Pesticide Residue Detection of Ministry of Agriculture, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou, 310021, Zhejiang, China.
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11
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Zhao B, Zhao B, Chen F. Diagnostic value of serum carbohydrate antigen 19-9 in pancreatic cancer: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2022; 34:891-904. [PMID: 35913776 DOI: 10.1097/meg.0000000000002415] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
Carbohydrate antigen 19-9 (CA19-9) is the most widely used serum biomarker for detecting pancreatic cancer (PC). Since early diagnosis is important for improving PC prognosis, a comprehensive understanding of the diagnostic performance of CA19-9 is critical. This study focused on comprehensive evaluation of the efficacy of CA19-9 in PC diagnosis. Literature research was based on the seven databases. Studies released from January 2002 to January 2022 focused on the efficacy of CA19-9 in the detection of PC were included. Summarized sensitivity, specificity, and sROC/accuracy of discrimination (AUC) were estimated. Potential publication bias was measured with Funnel plot and Egger's test. Meta-regression was performed to detect possible causes of heterogeneity. Subgroup analysis was used to assess the diagnostic efficacy of CA19-9 under different conditions. The study is registered on PROSPERO (CRD42021253861). Seventy-nine studies containing 20 991 participants who met the criteria were included. The pooled sensitivity, specificity, and AUC of CA19-9 in diagnose PC were 72% (95% CI, 71-73%), 86% (95% CI, 85-86%), and 0.8474 (95% CI, 0.8272-0.8676). Subgroup analysis suggested that the diagnostic efficiency of CA19-9 in studies with healthy controls was the highest, followed by intraductal papillary mucinous neoplasm, in pancreatitis and diabetes were consistent with the overall result. Our analysis showed that serum CA19-9 had high and stable diagnostic efficacy for PC (not affected by diabetes). Subgroup analysis showed that serum CA19-9 yielded highest effectiveness in the diagnosis of pancreatic precancerous lesions, which indicated an irreplaceable clinical value in the early detection and warning value for PC.
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Affiliation(s)
- Boqiang Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- The First School of Clinical Medicine, Xi'an, China
| | - Boyue Zhao
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
| | - Fangyao Chen
- Xi'an Jiaotong University Health Science Center, Xi'an, China
- Department of Epidemiology and Biostatistics, School of Public Health, Xi'an, China
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12
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Ketavarapu V, Ravikanth V, Sasikala M, Rao GV, Devi CV, Sripadi P, Bethu MS, Amanchy R, Murthy HVV, Pandol SJ, Reddy DN. Integration of metabolites from meta-analysis with transcriptome reveals enhanced SPHK1 in PDAC with a background of pancreatitis. BMC Cancer 2022; 22:792. [PMID: 35854233 PMCID: PMC9295503 DOI: 10.1186/s12885-022-09816-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 06/22/2022] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Pathophysiology of transformation of inflammatory lesions in chronic pancreatitis (CP) to pancreatic ductal adenocarcinoma (PDAC) is not clear. METHODS We conducted a systematic review, meta-analysis of circulating metabolites, integrated this data with transcriptome analysis of human pancreatic tissues and validated using immunohistochemistry. Our aim was to establish biomarker signatures for early malignant transformation in patients with underlying CP and identify therapeutic targets. RESULTS Analysis of 19 studies revealed AUC of 0.86 (95% CI 0.81-0.91, P < 0.0001) for all the altered metabolites (n = 88). Among them, lipids showed higher differentiating efficacy between PDAC and CP; P-value (< 0.0001). Pathway enrichment analysis identified sphingomyelin metabolism (impact value-0.29, FDR of 0.45) and TCA cycle (impact value-0.18, FDR of 0.06) to be prominent pathways in differentiating PDAC from CP. Mapping circulating metabolites to corresponding genes revealed 517 altered genes. Integration of these genes with transcriptome data of CP and PDAC with a background of CP (PDAC-CP) identified three upregulated genes; PIGC, PPIB, PKM and three downregulated genes; AZGP1, EGLN1, GNMT. Comparison of CP to PDAC-CP and PDAC-CP to PDAC identified upregulation of SPHK1, a known oncogene. CONCLUSIONS Our analysis suggests plausible role for SPHK1 in development of pancreatic adenocarcinoma in long standing CP patients. SPHK1 could be further explored as diagnostic and potential therapeutic target.
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Affiliation(s)
- Vijayasarathy Ketavarapu
- grid.410866.d0000 0004 1803 177XAsian Healthcare Foundation, Asian Institute of Gastroenterology, Mindspace Rd, Gachibowli, Hyderabad, Telangana 500032 India
| | - Vishnubhotla Ravikanth
- grid.410866.d0000 0004 1803 177XAsian Healthcare Foundation, Asian Institute of Gastroenterology, Mindspace Rd, Gachibowli, Hyderabad, Telangana 500032 India
| | - Mitnala Sasikala
- grid.410866.d0000 0004 1803 177XAsian Healthcare Foundation, Asian Institute of Gastroenterology, Mindspace Rd, Gachibowli, Hyderabad, Telangana 500032 India
| | - G. V. Rao
- grid.410866.d0000 0004 1803 177XAIG Hospitals, Mindspace Rd, Gachibowli, Hyderabad, Telangana 500032 India
| | - Ch. Venkataramana Devi
- grid.412419.b0000 0001 1456 3750Department of Biochemistry, University College of Science, Osmania University, Hyderabad, 500 007 India
| | - Prabhakar Sripadi
- grid.417636.10000 0004 0636 1405Centre for Mass Spectrometry, Analytical & Structural Chemistry Department, CSIR-Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 007 India
| | - Murali Satyanarayana Bethu
- grid.410865.eDivision of Applied Biology, CSIR-IICT (Indian Institute of Chemical Technology), Ministry of Science and Technology (GOI), Hyderabad, Telangana 500007 India ,grid.240614.50000 0001 2181 8635Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Elm &Carlton Streets, Buffalo, New York, 14221 USA
| | - Ramars Amanchy
- grid.410865.eDivision of Applied Biology, CSIR-IICT (Indian Institute of Chemical Technology), Ministry of Science and Technology (GOI), Hyderabad, Telangana 500007 India
| | - H. V. V. Murthy
- grid.410866.d0000 0004 1803 177XAsian Healthcare Foundation, Asian Institute of Gastroenterology, Mindspace Rd, Gachibowli, Hyderabad, Telangana 500032 India
| | - Stephen J. Pandol
- grid.50956.3f0000 0001 2152 9905Department of Medicine, Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA USA
| | - D. Nageshwar Reddy
- grid.410866.d0000 0004 1803 177XAIG Hospitals, Mindspace Rd, Gachibowli, Hyderabad, Telangana 500032 India
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13
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Xue L, Xu J, Feng C, Lu D, Zhou Z. Optimal Normalization Method for GC-MS/MS-Based Large-Scale Targeted Metabolomics. JOURNAL OF ANALYTICAL CHEMISTRY 2022. [DOI: 10.1134/s1061934822030054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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14
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Iwano T, Yoshimura K, Watanabe G, Saito R, Kiritani S, Kawaida H, Moriguchi T, Murata T, Ogata K, Ichikawa D, Arita J, Hasegawa K, Takeda S. High-performance Collective Biomarker from Liquid Biopsy for Diagnosis of Pancreatic Cancer Based on Mass Spectrometry and Machine Learning. J Cancer 2022; 12:7477-7487. [PMID: 35003367 PMCID: PMC8734412 DOI: 10.7150/jca.63244] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/12/2021] [Indexed: 02/07/2023] Open
Abstract
Background: Most pancreatic cancers are found at progressive stages when they cannot be surgically removed. Therefore, a highly accurate early detection method is urgently needed. Methods: This study analyzed serum from Japanese patients who suffered from pancreatic ductal adenocarcinoma (PDAC) and aimed to establish a PDAC-diagnostic system with metabolites in serum. Two groups of metabolites, primary metabolites (PM) and phospholipids (PL), were analyzed using liquid chromatography/electrospray ionization mass spectrometry. A support vector machine was employed to establish a machine learning-based diagnostic algorithm. Results: Integrating PM and PL databases improved cancer diagnostic accuracy and the area under the receiver operating characteristic curve. It was more effective than the algorithm based on either PM or PL database, or single metabolites as a biomarker. Subsequently, 36 statistically significant metabolites were fed into the algorithm as a collective biomarker, which improved results by accomplishing 97.4% and was further validated by additional serum. Interestingly, specific clusters of metabolites from patients with preoperative neoadjuvant chemotherapy (NAC) showed different patterns from those without NAC and were somewhat comparable to those of the control. Conclusion: We propose an efficient screening system for PDAC with high accuracy by liquid biopsy and potential biomarkers useful for assessing NAC performance.
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Affiliation(s)
- Tomohiko Iwano
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Kentaro Yoshimura
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Genki Watanabe
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Ryo Saito
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Sho Kiritani
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Hiromichi Kawaida
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Takeshi Moriguchi
- Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | | | | | - Daisuke Ichikawa
- First Department of Surgery, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
| | - Junichi Arita
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Kiyoshi Hasegawa
- Hepato-Biliary-Pancreatic Surgery Division, Department of Surgery, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Sen Takeda
- Department of Anatomy and Cell Biology, Faculty of Medicine, University of Yamanashi, Chuo, Yamanashi, Japan
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15
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Gould O, Drabińska N, Ratcliffe N, de Lacy Costello B. Hyphenated Mass Spectrometry versus Real-Time Mass Spectrometry Techniques for the Detection of Volatile Compounds from the Human Body. Molecules 2021; 26:molecules26237185. [PMID: 34885767 PMCID: PMC8659178 DOI: 10.3390/molecules26237185] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 11/22/2021] [Accepted: 11/23/2021] [Indexed: 01/16/2023] Open
Abstract
Mass spectrometry (MS) is an analytical technique that can be used for various applications in a number of scientific areas including environmental, security, forensic science, space exploration, agri-food, and numerous others. MS is also continuing to offer new insights into the proteomic and metabolomic fields. MS techniques are frequently used for the analysis of volatile compounds (VCs). The detection of VCs from human samples has the potential to aid in the diagnosis of diseases, in monitoring drug metabolites, and in providing insight into metabolic processes. The broad usage of MS has resulted in numerous variations of the technique being developed over the years, which can be divided into hyphenated and real-time MS techniques. Hyphenated chromatographic techniques coupled with MS offer unparalleled qualitative analysis and high accuracy and sensitivity, even when analysing complex matrices (breath, urine, stool, etc.). However, these benefits are traded for a significantly longer analysis time and a greater need for sample preparation and method development. On the other hand, real-time MS techniques offer highly sensitive quantitative data. Additionally, real-time techniques can provide results in a matter of minutes or even seconds, without altering the sample in any way. However, real-time MS can only offer tentative qualitative data and suffers from molecular weight overlap in complex matrices. This review compares hyphenated and real-time MS methods and provides examples of applications for each technique for the detection of VCs from humans.
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Affiliation(s)
- Oliver Gould
- Centre for Research in Biosciences, Frenchay Campus, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK; (N.R.); (B.d.L.C.)
- Correspondence: (O.G.); (N.D.)
| | - Natalia Drabińska
- Department of Chemistry and Biodynamics of Food, Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748 Olsztyn, Poland
- Food Volatilomics and Sensomics Group, Faculty of Food Science and Nutrition, Poznan University of Life Sciences, 60-637 Poznan, Poland
- Correspondence: (O.G.); (N.D.)
| | - Norman Ratcliffe
- Centre for Research in Biosciences, Frenchay Campus, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK; (N.R.); (B.d.L.C.)
| | - Ben de Lacy Costello
- Centre for Research in Biosciences, Frenchay Campus, University of the West of England, Coldharbour Lane, Bristol BS16 1QY, UK; (N.R.); (B.d.L.C.)
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16
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Saigusa D, Matsukawa N, Hishinuma E, Koshiba S. Identification of biomarkers to diagnose diseases and find adverse drug reactions by metabolomics. Drug Metab Pharmacokinet 2020; 37:100373. [PMID: 33631535 DOI: 10.1016/j.dmpk.2020.11.008] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2020] [Revised: 11/24/2020] [Accepted: 11/25/2020] [Indexed: 12/12/2022]
Abstract
Metabolomics has been widely used for investigating the biological functions of disease expression and has the potential to discover biomarkers in circulating biofluids or tissue extracts that reflect in phenotypic changes. Metabolic profiling has advantages because of the use of unbiased techniques, including multivariate analysis, and has been applied in pharmacological studies to predict therapeutic and adverse reactions of drugs, which is called pharmacometabolomics (PMx). Nuclear magnetic resonance (NMR)- and mass spectrometry (MS)-based metabolomics has contributed to the discovery of recent disease biomarkers; however, the optimal strategy for the study purpose must be selected from many established protocols, methodologies and analytical platforms. Additionally, information on molecular localization in tissue is essential for further functional analyses related to therapeutic and adverse effects of drugs in the process of drug development. MS imaging (MSI) is a promising technology that can visualize molecules on tissue surfaces without labeling and thus provide localized information. This review summarizes recent uses of MS-based global and wide-targeted metabolomics technologies and the advantages of the MSI approach for PMx and highlights the PMx technique for the biomarker discovery of adverse drug effects.
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Affiliation(s)
- Daisuke Saigusa
- Department of Integrative Genomics, Tohoku University Tohoku Medical Megabank Organization, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
| | - Naomi Matsukawa
- Department of Integrative Genomics, Tohoku University Tohoku Medical Megabank Organization, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
| | - Eiji Hishinuma
- Department of Integrative Genomics, Tohoku University Tohoku Medical Megabank Organization, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
| | - Seizo Koshiba
- Department of Integrative Genomics, Tohoku University Tohoku Medical Megabank Organization, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan; Medical Biochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan; Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8573, Japan.
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17
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Zhang WH, Wang WQ, Han X, Gao HL, Li TJ, Xu SS, Li S, Xu HX, Li H, Ye LY, Lin X, Wu CT, Long J, Yu XJ, Liu L. Advances on diagnostic biomarkers of pancreatic ductal adenocarcinoma: A systems biology perspective. Comput Struct Biotechnol J 2020; 18:3606-3614. [PMID: 33304458 PMCID: PMC7710502 DOI: 10.1016/j.csbj.2020.11.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 11/08/2020] [Accepted: 11/10/2020] [Indexed: 12/26/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is usually diagnosed at an advanced stage when curative surgery is no longer an option. Robust diagnostic biomarkers with high sensitivity and specificity for early detection are urgently needed. Systems biology provides a powerful tool for understanding diseases and solving challenging biological problems, allowing biomarkers to be identified and quantified with increasing accuracy, sensitivity, and comprehensiveness. Here, we present a comprehensive overview of efforts to identify biomarkers of PDAC using genomics, transcriptomics, proteomics, metabonomics, and bioinformatics. Systems biology perspective provides a crucial “network” to integrate multi-omics approaches to biomarker identification, shedding additional light on early PDAC detection.
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Affiliation(s)
- Wu-Hu Zhang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Wen-Quan Wang
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xuan Han
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - He-Li Gao
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Tian-Jiao Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Shuai-Shuai Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Shuo Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Hua-Xiang Xu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Hao Li
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Long-Yun Ye
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xuan Lin
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Chun-Tao Wu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Jiang Long
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xian-Jun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Liang Liu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Shanghai Pancreatic Cancer Institute, Shanghai, China.,Pancreatic Cancer Institute, Fudan University, Shanghai, China
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18
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Nakano R, Nishiumi S, Kobayashi T, Ikegawa T, Kodama Y, Yoshida M. Possibility of detecting intraductal papillary mucinous neoplasms using metabolite biomarkers for pancreatic cancer. Biomark Med 2020; 14:1009-1020. [PMID: 32940075 DOI: 10.2217/bmm-2019-0587] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2019] [Accepted: 06/05/2020] [Indexed: 12/28/2022] Open
Abstract
Aim: The aim of this study was to identify whether metabolite biomarker candidates for pancreatic cancer (PC) could aid detection of intraductal papillary mucinous neoplasms (IPMN), recognized as high-risk factors for PC. Materials & methods: The 12 metabolite biomarker candidates, which were found to be useful to detect PC in our previous study, were evaluated for plasma samples from patients with PC (n = 44) or IPMN (n = 24) or healthy volunteers (n = 46). Results: Regarding the performance of individual biomarkers of PC and PC high-risk IPMN, lysine exhibited the best performance (sensitivity: 67.8%; specificity: 86.9%). The multiple logistic regression analysis-based detection model displayed high sensitivity and specificity values of 92.5 and 90.6%, respectively. Conclusion: Metabolite biomarker candidates for PC are useful for detecting high-risk IPMN, which can progress to PC.
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Affiliation(s)
- Ryota Nakano
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Shin Nishiumi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
- Department of Omics Medicine, Hyogo College of Medicine, Nishinomiya, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Takuya Ikegawa
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Yuzo Kodama
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Masaru Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
- Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Hyogo, Japan
- AMED-CREST, AMED, Hyogo, Japan
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19
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Kriz D, Ansari D, Andersson R. Potential biomarkers for early detection of pancreatic ductal adenocarcinoma. Clin Transl Oncol 2020; 22:2170-2174. [PMID: 32447642 PMCID: PMC7578134 DOI: 10.1007/s12094-020-02372-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2020] [Accepted: 05/01/2020] [Indexed: 12/12/2022]
Abstract
Pancreatic cancer has the highest mortality amongst all major organ cancers. Early detection is key to reduce deaths related to pancreatic cancer. However, early detection has been challenged by the lack of non-invasive biomarkers with enough sensitivity and specificity to allow for screening. The gold standard is still carbohydrate antigen (CA 19-9), against which all new biomarkers must be evaluated. In this paper, we describe recent progress in the development of new pancreatic cancer biomarkers, focusing on proteins, metabolites, and genetic and epigenetic biomarkers. Although several promising biomarkers have been identified, they are all derived from retrospective studies and additional prospective studies are needed to confirm their clinical validity.
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Affiliation(s)
- D Kriz
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
| | - D Ansari
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden
| | - R Andersson
- Department of Surgery, Clinical Sciences Lund, Skåne University Hospital, Lund University, Lund, Sweden.
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20
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Zhang X, Shi X, Lu X, Li Y, Zhan C, Akhtar ML, Yang L, Bai Y, Zhao J, Wang Y, Yao Y, Li Y, Nie H. Novel Metabolomics Serum Biomarkers for Pancreatic Ductal Adenocarcinoma by the Comparison of Pre-, Postoperative and Normal Samples. J Cancer 2020; 11:4641-4651. [PMID: 32626510 PMCID: PMC7330680 DOI: 10.7150/jca.41250] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 04/14/2020] [Indexed: 12/11/2022] Open
Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies. The metabolomic approaches are developed to discover the novel biomarkers of PDAC. Methods: 550 preoperative, postoperative PDAC and normal controls (NCs) serums were employed to characterize metabolic alterations in training and validation sets by LC-MS. Results: The results of PLS-DA analysis indicated that three groups could be distinguished clearly and the post-PDAC group is adjacent to a normal group as compared with pre-PDAC group. Further results showed that histidinyl-lysine significantly increased whereas docosahexaenoic acid and LysoPC (14:0) decreased in pre-PDAC patients as compared with NCs. And these three markers had a significant tendency to recover after tumor resection. The validation set results revealed that for CA19-9 negative patients, 92.3% (12/13) of them can be screened using these three metabolites. The combination of these markers could significantly improve the diagnostic performance for PDAC, with higher sensitivity (0.93), specificity (0.92) and AUC (0.97). Moreover, network and pathways analyses explored the latent relationship among differential metabolites. The glycerolipid metabolism and primary bile acid synthesis showed variation in network and pathway analysis. Conclusions: These three markers combined with CA199 displayed high sensitivity and specificity for detecting PDAC patients from NCs. The results indicated that these three metabolites could be regarded as potential biomarkers to distinguish PDAC from NCs.
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Affiliation(s)
- Xiaohan Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Xiuyun Shi
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Xin Lu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yiqun Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Chao Zhan
- The Affiliated Tumor Hospital, Harbin Medical University, Harbin, China
| | | | - Lijun Yang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yunfan Bai
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Jianxiang Zhao
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yu Wang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Yuanfei Yao
- The Affiliated Tumor Hospital, Harbin Medical University, Harbin, China
| | - Yu Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
| | - Huan Nie
- School of Life Science and Technology, Harbin Institute of Technology, Harbin, China
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21
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Lee HK, Kim K, Lee J, Lee J, Lee J, Kim S, Lee SE, Kim JH. Targeted toxicometabolomics of endosulfan sulfate in adult zebrafish (Danio rerio) using GC-MS/MS in multiple reaction monitoring mode. JOURNAL OF HAZARDOUS MATERIALS 2020; 389:122056. [PMID: 32000124 DOI: 10.1016/j.jhazmat.2020.122056] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 12/16/2019] [Accepted: 01/08/2020] [Indexed: 06/10/2023]
Abstract
Endosulfan sulfate is a major oxidative metabolite of the chlorinated insecticide endosulfan. In this study, a targeted metabolomics approach was used to investigate the toxic mechanisms of endosulfan sulfate in adult zebrafish using the multiple reaction monitoring mode of a GC-MS/MS. The LC50 of endosulfan sulfate in adult zebrafish was determined and then zebrafish were exposed to endosulfan sulfate at one-tenth the LC50 (0.1LC50) or the LC50 for 24 and 48 h. After exposure, the fish were extracted, derivatized and analyzed by GC-MS/MS for 379 metabolites to identify 170 metabolites. Three experimental groups (control, 0.1LC50 and LC50) were clearly separated in PLS-DA score plots. Based on the VIP, ANOVA, and fold change results, 40 metabolites were selected as biomarkers. Metabolic pathways associated with those metabolites were identified using MetaboAnalyst 4.0 as follows: aminoacyl-tRNA biosynthesis, valine/leucine/isoleucine biosynthesis, citrate cycle, glycerolipid metabolism, and arginine/proline metabolism. Gene expression studies confirmed the activation of citrate cycle and glycerolipids metabolism. MDA levels of the exposed group significantly increased in oxidative toxicity assay tests. Such significant perturbations of important metabolites within key biochemical pathways must result in biologically hazardous effects in zebrafish.
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Affiliation(s)
- Hwa-Kyung Lee
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea
| | - Kyeongnam Kim
- School of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea
| | - Junghak Lee
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea
| | - Jonghwa Lee
- Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, MA, 01003, USA
| | - Jiho Lee
- Environmental Medical Center, Korea Conformity Laboratories, Incheon, 21999, Republic of Korea
| | - Sooyeon Kim
- Gyeongnam Department of Environmental Toxicology and Chemistry, Korea Institute of Toxicology, Gyeongsangnam-do, 52834, Republic of Korea
| | - Sung-Eun Lee
- School of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
| | - Jeong-Han Kim
- Department of Agricultural Biotechnology and Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.
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22
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Carmicheal J, Patel A, Dalal V, Atri P, Dhaliwal AS, Wittel UA, Malafa MP, Talmon G, Swanson BJ, Singh S, Jain M, Kaur S, Batra SK. Elevating pancreatic cystic lesion stratification: Current and future pancreatic cancer biomarker(s). Biochim Biophys Acta Rev Cancer 2019; 1873:188318. [PMID: 31676330 DOI: 10.1016/j.bbcan.2019.188318] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2019] [Revised: 10/25/2019] [Accepted: 10/25/2019] [Indexed: 02/06/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an incredibly deadly disease with a 5-year survival rate of 9%. The presence of pancreatic cystic lesions (PCLs) confers an increased likelihood of future pancreatic cancer in patients placing them in a high-risk category. Discerning concurrent malignancy and risk of future PCL progression to cancer must be carefully and accurately determined to improve survival outcomes and avoid unnecessary morbidity of pancreatic resection. Unfortunately, current image-based guidelines are inadequate to distinguish benign from malignant lesions. There continues to be a need for accurate molecular and imaging biomarker(s) capable of identifying malignant PCLs and predicting the malignant potential of PCLs to enable risk stratification and effective intervention management. This review provides an update on the current status of biomarkers from pancreatic cystic fluid, pancreatic juice, and seromic molecular analyses and discusses the potential of radiomics for differentiating PCLs harboring cancer from those that do not.
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Affiliation(s)
- Joseph Carmicheal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Asish Patel
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Surgery, University of Nebraska Medical Center, Omaha, NE, USA
| | - Vipin Dalal
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Pranita Atri
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Amaninder S Dhaliwal
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Uwe A Wittel
- Department of General- and Visceral Surgery, University of Freiburg Medical Center, Faculty of Medicine, Freiburg, Germany
| | - Mokenge P Malafa
- Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
| | - Geoffrey Talmon
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Benjamin J Swanson
- Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Shailender Singh
- Department of Internal Medicine, Division of Gastroenterology-Hepatology, University of Nebraska Medical Center, Omaha, NE, USA
| | - Maneesh Jain
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
| | - Sukhwinder Kaur
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
| | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA; Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA; Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA; Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
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23
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Nambu M, Masuda T, Ito S, Kato K, Kojima T, Daiko H, Ito Y, Honda K, Ohtsuki S. Leucine-Rich Alpha-2-Glycoprotein 1 in Serum Is a Possible Biomarker to Predict Response to Preoperative Chemoradiotherapy for Esophageal Cancer. Biol Pharm Bull 2019; 42:1766-1771. [DOI: 10.1248/bpb.b19-00395] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Madoka Nambu
- Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University
| | - Takeshi Masuda
- Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University
- Faculty of Life Sciences, Kumamoto University
- AMED-CREST, Japan Agency for Medical Research and Development
| | - Shingo Ito
- Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University
- Faculty of Life Sciences, Kumamoto University
- AMED-CREST, Japan Agency for Medical Research and Development
| | - Ken Kato
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital
| | - Takashi Kojima
- Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East
| | - Hiroyuki Daiko
- Division of Gastrointestinal Oncology, National Cancer Center Hospital
| | - Yoshinori Ito
- Department of Radiation Oncology, Showa University School of Medicine
| | - Kazufumi Honda
- AMED-CREST, Japan Agency for Medical Research and Development
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute
| | - Sumio Ohtsuki
- Department of Pharmaceutical Microbiology, School of Pharmacy, Kumamoto University
- Faculty of Life Sciences, Kumamoto University
- AMED-CREST, Japan Agency for Medical Research and Development
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24
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Kobayashi T, Honda K. Trends in biomarker discoveries for the early detection and risk stratification of pancreatic cancer using omics studies. Expert Rev Mol Diagn 2019; 19:651-654. [PMID: 31298060 DOI: 10.1080/14737159.2019.1643718] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Affiliation(s)
- Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine , Kobe , Hyogo , Japan
| | - Kazufumi Honda
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute , Tokyo , Japan
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25
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Farley AM, Braxton DR, Li J, Trounson K, Sakar-Dey S, Nayer B, Ikeda T, Lau KX, Hardikar W, Hasegawa K, Pera MF. Antibodies to a CA 19-9 Related Antigen Complex Identify SOX9 Expressing Progenitor Cells In Human Foetal Pancreas and Pancreatic Adenocarcinoma. Sci Rep 2019; 9:2876. [PMID: 30814526 PMCID: PMC6393509 DOI: 10.1038/s41598-019-38988-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2017] [Accepted: 01/11/2019] [Indexed: 12/21/2022] Open
Abstract
The Sialyl Lewis A antigen, or CA 19-9, is the prototype serum biomarker for adenocarcinoma of the pancreas. Despite extensive clinical study of CA 19-9 in gastrointestinal malignancies, surprisingly little is known concerning the specific cell types that express this marker during development, tissue regeneration and neoplasia. SOX9 is a transcription factor that plays a key role in these processes in foregut tissues. We report the biochemistry and tissue expression of the GCTM-5 antigen, a pancreatic cancer marker related to, but distinct from, CA19-9. This antigen, defined by two monoclonal antibodies recognising separate epitopes on a large glycoconjugate protein complex, is co-expressed with SOX9 by foregut ductal progenitors in the developing human liver and pancreas, and in pancreatic adenocarcinoma. These progenitors are distinct from cell populations identified by DCLK1, LGR5, or canonical markers of liver and pancreatic progenitor cells. Co-expression of this antigen complex and SOX9 also characterises the ductal metaplasia of submucosal glands that occurs during the development of Barrett’s oesophagus. The GCTM-5 antigen complex can be detected in the sera of patients with pancreatic adenocarcinoma. The GCTM-5 epitope shows a much more restricted pattern of expression in the normal adult pancreas relative to CA19-9. Our findings will aid in the identification, characterisation, and monitoring of ductal progenitor cells during development and progression of pancreatic adenocarcinoma in man.
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Affiliation(s)
- Alison M Farley
- Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia.,The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
| | - David R Braxton
- Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA
| | - Jonathan Li
- Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia
| | - Karl Trounson
- Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia
| | | | - Bhavana Nayer
- Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India
| | - Tatsuhiko Ikeda
- Institute for Integrated Cell-Materials Science, Kyoto University, Kyoto, Japan
| | - Kevin X Lau
- Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia
| | - Winita Hardikar
- Royal Childrens Hospital, Parkville, Victoria, Australia.,Childrens Medical Research Institute, Parkville, Victoria, Australia
| | - Kouichi Hasegawa
- Institute for Stem Cell Biology and Regenerative Medicine, Bangalore, India.,Institute for Integrated Cell-Materials Science, Kyoto University, Kyoto, Japan
| | - Martin F Pera
- Department of Anatomy and Neuroscience, University of Melbourne, Melbourne, Victoria, Australia. .,Florey Neuroscience and Mental Health Institute, Parkville, Victoria, Australia. .,The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
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26
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Husi H, Fernandes M, Skipworth RJ, Miller J, Cronshaw AD, Fearon KCH, Ross JA. Identification of diagnostic upper gastrointestinal cancer tissue type-specific urinary biomarkers. Biomed Rep 2019; 10:165-174. [PMID: 30906545 PMCID: PMC6423495 DOI: 10.3892/br.2019.1190] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Accepted: 01/02/2019] [Indexed: 02/07/2023] Open
Abstract
Several potential urinary biomarkers exhibiting an association with upper gastrointestinal tumour growth have been previously identified, of which S100A6, S100A9, rabenosyn-5 and programmed cell death 6-interacting protein (PDCD6IP) were further validated and found to be upregulated in malignant tumours. The cancer cohort from our previous study was subclassified to assess whether distinct molecular markers can be identified for each individual cancer type using a similar approach. Urine samples from patients with cancers of the stomach, oesophagus, oesophagogastric junction or pancreas were analysed by surface-enhanced laser desorption/ionization-time-of-flight mass spectrometry using both CM10 and IMAC30 (Cu2+-complexed) chip types and LC-MS/MS-based mass spectrometry after chromatographic enrichment. This was followed by protein identification, pattern matching and validation by western blotting. We found 8 m/z peaks with statistical significance for the four cancer types investigated, of which m/z 2447 and 2577 were identified by pattern matching as fragments of cathepsin-B (CTSB) and cystatin-B (CSTB); both molecules are indicative of pancreatic cancer. Additionally, we observed a potential association of upregulated α-1-antichymotrypsin with pancreatic and gastric cancers, of PDCD6IP, vitelline membrane outer layer protein 1 homolog (VMO1) and triosephosphate isomerase (TPI1) with oesophagogastric junctional cancers, and of complement C4-A, prostatic acid phosphatase, azurocidin and histone-H1 with oesophageal cancer. Furthermore, the potential pancreatic cancer biomarkers CSTB and CTSB were validated independently by western blotting. Therefore, the present study identified two new potential urinary biomarkers that appear to be associated with pancreatic cancer. This may provide a simple, non-invasive screening test for use in the clinical setting.
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Affiliation(s)
- Holger Husi
- Department of Diabetes and Cardiovascular Science, University of the Highlands and Islands, Inverness IV2 3JH, UK.,BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK.,School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Marco Fernandes
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK
| | - Richard J Skipworth
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Janice Miller
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Andrew D Cronshaw
- School of Biological Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - Kenneth C H Fearon
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
| | - James A Ross
- School of Clinical Sciences and Community Health, University of Edinburgh, Edinburgh EH16 4SB, UK
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27
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Jiao L, Maity S, Coarfa C, Rajapakshe K, Chen L, Jin F, Putluri V, Tinker LF, Mo Q, Chen F, Sen S, Sangi-Hyghpeykar H, El-Serag HB, Putluri N. A Prospective Targeted Serum Metabolomics Study of Pancreatic Cancer in Postmenopausal Women. Cancer Prev Res (Phila) 2019; 12:237-246. [PMID: 30723176 DOI: 10.1158/1940-6207.capr-18-0201] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2018] [Revised: 11/12/2018] [Accepted: 01/29/2019] [Indexed: 12/11/2022]
Abstract
To examine the association between metabolic deregulation and pancreatic cancer, we conducted a two-stage case-control targeted metabolomics study using prediagnostic sera collected one year before diagnosis in the Women's Health Initiative study. We used the LC/MS to quantitate 470 metabolites in 30 matched case/control pairs. From 180 detectable metabolites, we selected 14 metabolites to be validated in additional 18 matched case/control pairs. We used the paired t test to compare the concentrations of each metabolite between cases and controls and used the log fold change (FC) to indicate the magnitude of difference. FDR adjusted q-value < 0.25 was indicated statistically significant. Logistic regression model and ROC curve analysis were used to evaluate the clinical utility of the metabolites. Among 30 case/control pairs, 1-methyl-l-tryptophan (L-1MT) was significantly lower in the cases than in the controls (log2 FC = -0.35; q-value = 0.03). The area under the ROC curve was 0.83 in the discrimination analysis based on the levels of L-1MT, acadesine, and aspartic acid. None of the metabolites was validated in additional independent 18 case/control pairs. No significant association was found between the examined metabolites and undiagnosed pancreatic cancer.
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Affiliation(s)
- Li Jiao
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas. .,Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, Texas.,Advanced Technology Core, Baylor College of Medicine, Houston, Texas.,Department of Molecular & Cell Biology, Baylor College of Medicine, Houston, Texas.,Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
| | - Suman Maity
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Cristian Coarfa
- Advanced Technology Core, Baylor College of Medicine, Houston, Texas.,Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | | | - Liang Chen
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.,Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, Texas
| | - Feng Jin
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Vasanta Putluri
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Lesley F Tinker
- Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, Texas
| | - Qianxing Mo
- Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas
| | - Fengju Chen
- Advanced Technology Core, Baylor College of Medicine, Houston, Texas
| | - Subrata Sen
- Department of Translational Molecular Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
| | | | - Hashem B El-Serag
- Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, Texas.,Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, Texas.,Advanced Technology Core, Baylor College of Medicine, Houston, Texas.,Department of Molecular & Cell Biology, Baylor College of Medicine, Houston, Texas
| | - Nagireddy Putluri
- Advanced Technology Core, Baylor College of Medicine, Houston, Texas.,Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, Texas.,Texas Medical Center Digestive Disease Center, Houston, Texas
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28
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Wen J, Yang L, Qin F, Zhao L, Xiong Z. An integrative UHPLC-MS/MS untargeted metabonomics combined with quantitative analysis of the therapeutic mechanism of Si-Ni-San. Anal Biochem 2019; 567:128-135. [DOI: 10.1016/j.ab.2018.10.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2018] [Revised: 10/18/2018] [Accepted: 10/22/2018] [Indexed: 02/07/2023]
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29
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Iemoto T, Nishiumi S, Kobayashi T, Fujigaki S, Hamaguchi T, Kato K, Shoji H, Matsumura Y, Honda K, Yoshida M. Serum level of octanoic acid predicts the efficacy of chemotherapy for colorectal cancer. Oncol Lett 2018; 17:831-842. [PMID: 30655836 PMCID: PMC6312949 DOI: 10.3892/ol.2018.9731] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2018] [Accepted: 09/19/2018] [Indexed: 12/18/2022] Open
Abstract
The survival times of patients with advanced colorectal cancer (CRC) have increased due to the introduction of chemotherapy involving irinotecan and cetuximab. However, further studies are required on the effective pretreatment methods for identifying patients with CRC who would respond to particular treatments. The aim of the present study was to identify biomarkers for predicting the efficacy of chemotherapy for CRC. A total of 123 serum samples were collected from 31 patients with CRC just prior to each of the first four rounds of chemotherapy. Serum metabolome analysis was performed using a multiplatform metabolomics system, and univariate Cox regression hazards analysis of the time to disease progression was conducted. Octanoic acid and 1,5-anhydro-D-glucitol were identified as biomarker candidates. In addition, the serum level of octanoic acid was indicated to be significantly associated with the time to disease progression (hazard ratio, 3.3; 95% confidence interval, 1.099–11.840; P=0.033). The serum levels of fatty acids, in particular polyunsaturated fatty acids, tended to be downregulated in the partial response group. The findings of the present study suggest that the serum level of octanoic acid may serve as a useful predictor for the prognosis of CRC.
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Affiliation(s)
- Takao Iemoto
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Shin Nishiumi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Seiji Fujigaki
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan
| | - Tetsuya Hamaguchi
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Ken Kato
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Hirokazu Shoji
- Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo 104-0045, Japan
| | - Yasuhiro Matsumura
- Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba 277-8577, Japan
| | - Kazufumi Honda
- Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo 104-0045, Japan
| | - Masaru Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.,Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Hyogo 650-0017, Japan.,AMED-CREST, AMED, Kobe, Hyogo 650-0017, Japan
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30
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Miyagawa H, Bamba T. Comparison of sequential derivatization with concurrent methods for GC/MS-based metabolomics. J Biosci Bioeng 2018; 127:160-168. [PMID: 30316697 DOI: 10.1016/j.jbiosc.2018.07.015] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 06/17/2018] [Accepted: 07/16/2018] [Indexed: 11/16/2022]
Abstract
The gas chromatography/mass spectrometry (GC/MS)-based metabolomics requires a two-step derivatization procedure consisting of oximation and silylation. However, due to the incomplete derivatization and degeneration of the metabolites, good repeatability is difficult to obtain during the batch derivatization, as the time between completing the derivatization process and GC analysis differs from sample to sample. In this research, we successfully obtained good repeatability for the peak areas of 52 selected metabolites by sequential derivatization and interval injection, in which the oximation and silylation times were maintained at constant values. In addition, the derivatization times and amount of reagents employed were varied to confirm that the optimal derivatization conditions differed for the various metabolites. In conventional batch derivatization, six metabolites, viz. glutamine, glutamic acid, histidine, alanine, asparagine, and tryptophan, exhibited fluctuations in their peak areas. Indeed, we found that for all six metabolites these differences originated from the silylation process, while the variations for glutamine and glutamic acid were related to the oximation process.
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Affiliation(s)
- Hiromi Miyagawa
- GL Sciences Inc., 237-2 Sayamagahara, Iruma, Saitama 358-0032, Japan
| | - Takeshi Bamba
- Research Center for Transomics Medicine, Medical Institute of Bioregulation, Kyusyu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
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31
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Long NP, Yoon SJ, Anh NH, Nghi TD, Lim DK, Hong YJ, Hong SS, Kwon SW. A systematic review on metabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer. Metabolomics 2018; 14:109. [PMID: 30830397 DOI: 10.1007/s11306-018-1404-2] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Accepted: 07/31/2018] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Metabolomics is an emerging approach for early detection of cancer. Along with the development of metabolomics, high-throughput technologies and statistical learning, the integration of multiple biomarkers has significantly improved clinical diagnosis and management for patients. OBJECTIVES In this study, we conducted a systematic review to examine recent advancements in the oncometabolomics-based diagnostic biomarker discovery and validation in pancreatic cancer. METHODS PubMed, Scopus, and Web of Science were searched for relevant studies published before September 2017. We examined the study designs, the metabolomics approaches, and the reporting methodological quality following PRISMA statement. RESULTS AND CONCLUSION: The included 25 studies primarily focused on the identification rather than the validation of predictive capacity of potential biomarkers. The sample size ranged from 10 to 8760. External validation of the biomarker panels was observed in nine studies. The diagnostic area under the curve ranged from 0.68 to 1.00 (sensitivity: 0.43-1.00, specificity: 0.73-1.00). The effects of patients' bio-parameters on metabolome alterations in a context-dependent manner have not been thoroughly elucidated. The most reported candidates were glutamic acid and histidine in seven studies, and glutamine and isoleucine in five studies, leading to the predominant enrichment of amino acid-related pathways. Notably, 46 metabolites were estimated in at least two studies. Specific challenges and potential pitfalls to provide better insights into future research directions were thoroughly discussed. Our investigation suggests that metabolomics is a robust approach that will improve the diagnostic assessment of pancreatic cancer. Further studies are warranted to validate their validity in multi-clinical settings.
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Affiliation(s)
- Nguyen Phuoc Long
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Sang Jun Yoon
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Nguyen Hoang Anh
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Tran Diem Nghi
- School of Medicine, Vietnam National University, Ho Chi Minh City, 700000, Vietnam
| | - Dong Kyu Lim
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Yu Jin Hong
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea
| | - Soon-Sun Hong
- Department of Drug Development, College of Medicine, Inha University, Incheon, 22212, South Korea
| | - Sung Won Kwon
- Research Institute of Pharmaceutical Sciences and College of Pharmacy, Seoul National University, Seoul, 08826, South Korea.
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32
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Fujigaki S, Nishiumi S, Kobayashi T, Suzuki M, Iemoto T, Kojima T, Ito Y, Daiko H, Kato K, Shouji H, Honda K, Azuma T, Yoshida M. Identification of serum biomarkers of chemoradiosensitivity in esophageal cancer via the targeted metabolomics approach. Biomark Med 2018; 12:827-840. [PMID: 30043633 DOI: 10.2217/bmm-2017-0449] [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] [Indexed: 12/20/2022] Open
Abstract
AIM To identify the serum metabolomics signature that is correlated with the chemoradiosensitivity of esophageal squamous cell carcinoma (ESCC). MATERIALS & METHODS Untargeted and targeted metabolomics analysis of serum samples from 26 ESCC patients, which were collected before the neoadjuvant chemoradiotherapy, was performed. RESULTS On receiving the results of untargeted metabolomics analysis, we performed the targeted metabolomics analysis of the six metabolites (arabitol, betaine, glycine, L-serine, L-arginine and L-aspartate). The serum levels of the four metabolites (arabitol, glycine, L-serine and L-arginine) were significantly lower in the patients who achieved pathological complete response with neoadjuvant chemoradiotherapy compared with the patients who did not achieve pathological complete response (p = 0.0086, 0.0345, 0.0106 and 0.0373, respectively). CONCLUSION The serum levels of metabolites might be useful for predicting the chemoradiosensitivity of ESCC patients.
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Affiliation(s)
- Seiji Fujigaki
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Shin Nishiumi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Takashi Kobayashi
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Makoto Suzuki
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Takao Iemoto
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Takashi Kojima
- Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Chiba, Japan
| | - Yoshinori Ito
- Department of Radiation Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroyuki Daiko
- Department of Esophageal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Ken Kato
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Hirokazu Shouji
- Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Kazufumi Honda
- Department of Biomarkers for Early Detection of Cancer, National Cancer Center Research Institute, Tokyo, Japan
| | - Takeshi Azuma
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan
| | - Masaru Yoshida
- Division of Gastroenterology, Department of Internal Medicine, Kobe University Graduate School of Medicine, Hyogo, Japan.,Division of Metabolomics Research, Department of Internal Related, Kobe University Graduate School of Medicine, Kobe, Japan.,AMED-CREST, AMED, Kobe, Japan
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López-López Á, López-Gonzálvez Á, Barker-Tejeda TC, Barbas C. A review of validated biomarkers obtained through metabolomics. Expert Rev Mol Diagn 2018; 18:557-575. [PMID: 29808702 DOI: 10.1080/14737159.2018.1481391] [Citation(s) in RCA: 44] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Studying changes in the whole set of small molecules, final products of biochemical reactions in living systems or metabolites, is extremely appealing because they represent the best approach to identifying what occurs in an organism when samples are collected. However, their usefulness as potential biomarkers is limited by discoveries obtained in small groups without proper validation or even confirmation of the chemical structure. Areas covered: During the past 5 years, more than 900 papers have been published on metabolomics for biomarker discovery, but the numbers are much lower when some criteria of validation are applied. In total, 102 papers have been included in this review. The most frequent disease areas in which these markers have been discovered include the following: cancer, diabetes, and related diseases and neurodegenerative, cardiovascular, autoimmune, liver, and kidney diseases. Expert commentary: Metabolomics has been demonstrated as rapidly growing due to the improvements in instrumentation, mainly mass spectrometry, and data mining software. For application in the clinic, the results should be validated in different stages, from analytical validation to validation in independent sets of samples, using thousands of samples from different sources.
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Affiliation(s)
- Ángeles López-López
- a Centre for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia , Universidad CEU San Pablo , Madrid , Spain
| | - Ángeles López-Gonzálvez
- a Centre for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia , Universidad CEU San Pablo , Madrid , Spain
| | - Tomás Clive Barker-Tejeda
- a Centre for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia , Universidad CEU San Pablo , Madrid , Spain
| | - Coral Barbas
- a Centre for Metabolomics and Bioanalysis (CEMBIO), Facultad de Farmacia , Universidad CEU San Pablo , Madrid , Spain
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A prospective evaluation of serum kynurenine metabolites and risk of pancreatic cancer. PLoS One 2018; 13:e0196465. [PMID: 29734388 PMCID: PMC5937773 DOI: 10.1371/journal.pone.0196465] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2017] [Accepted: 04/15/2018] [Indexed: 01/12/2023] Open
Abstract
Background Serum pyridoxal 5’-phosphate (PLP), the active form of vitamin B6, is associated with reduced risk of pancreatic cancer. Data on functional measures of vitamin B6 status and risk of pancreatic cancer is lacking. Methods A nested case-control study involving 187 incident cases of pancreatic cancer and 362 individually matched controls were conducted within two prospective cohorts to evaluate the associations between kynurenine metabolites in pre-diagnostic serum samples and risk of pancreatic cancer. Results Higher serum concentrations of 3-hydroxyanthranilic acid (HAA) and the HAA:3-hydroxykynurenine (HK) ratio (a measure for in vivo functional status of PLP) were significantly associated with reduced risk of pancreatic cancer. Compared with the lowest tertile, odds ratios (95% confidence intervals) of pancreatic cancer for the highest tertile was 0.62 (0.39, 1.01) for HAA, and 0.59 (0.35–0.98) for the HAA:HK ratio, after adjustment for potential confounders and serum PLP (both Ps for trend<0.05). The kynurenine:tryptophan ratio or neopterin was not significantly associated with pancreatic cancer risk. Conclusions The inverse association between HAA or the HAA:HK ratio and risk of pancreatic cancer supports the notion that functional status of PLP may be a more important measure than circulating PLP alone for the development of pancreatic cancer.
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Nakagawa T, Kobayashi T, Nishiumi S, Hidaka A, Yamaji T, Sawada N, Hirata Y, Yamanaka K, Azuma T, Goto A, Shimazu T, Inoue M, Iwasaki M, Yoshida M, Tsugane S. Metabolome analysis for pancreatic cancer risk in nested case-control study: Japan Public Health Center-based prospective Study. Cancer Sci 2018; 109:1672-1681. [PMID: 29575390 PMCID: PMC5980145 DOI: 10.1111/cas.13573] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2017] [Revised: 03/05/2018] [Accepted: 03/09/2018] [Indexed: 01/05/2023] Open
Abstract
Discovery of a high-risk group for pancreatic cancer is important for prevention of pancreatic cancer. The present study was conducted as a nested case-control study including 170 pancreatic cancer cases and 340 matched controls of our population-based cohort study involving 30 239 subjects who answered a baseline questionnaire and supplied blood samples. Twelve targeted metabolites were quantitatively analyzed by gas chromatography/tandem mass spectrometry. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were calculated using conditional logistic regression models. Statistically significant P-value was defined as P < .05. Increasing 1,5-anhydro-d-glucitol (1,5-AG) levels were associated with a decreasing trend in pancreatic cancer risk (OR of quartile 4 [Q4], 0.50; 95% CI, 0.27-0.93; P = .02). Increasing methionine levels were also associated with an increasing trend of pancreatic cancer risk (OR of Q4, 1.79; 95% CI, 0.94-3.40: P = .03). Additional adjustment for potential confounders attenuated the observed associations of 1,5-AG and methionine (P for trend = .06 and .07, respectively). Comparing subjects diagnosed in the first 0-6 years, higher levels of 1,5-AG, asparagine, tyrosine and uric acid showed a decreasing trend for pancreatic cancer risk (P for trend = .04, .04, .04 and .02, respectively), even after adjustment for potential confounders. We found that the 12 target metabolites were not associated with pancreatic cancer risk. However, metabolic changes in the subjects diagnosed in the first 0-6 years showed a similar tendency to our previous reports. These results might suggest that these metabolites are useful for early detection but not for prediction of pancreatic cancer.
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Affiliation(s)
- Takashi Nakagawa
- Division of GastroenterologyDepartment of Internal MedicineKobe University Graduate School of MedicineHyogoJapan
| | - Takashi Kobayashi
- Division of GastroenterologyDepartment of Internal MedicineKobe University Graduate School of MedicineHyogoJapan
| | - Shin Nishiumi
- Division of GastroenterologyDepartment of Internal MedicineKobe University Graduate School of MedicineHyogoJapan
| | - Akihisa Hidaka
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Taiki Yamaji
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Norie Sawada
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Yuichi Hirata
- Division of GastroenterologyDepartment of Internal MedicineKobe University Graduate School of MedicineHyogoJapan
| | - Kodai Yamanaka
- Division of GastroenterologyDepartment of Internal MedicineKobe University Graduate School of MedicineHyogoJapan
| | - Takeshi Azuma
- Division of GastroenterologyDepartment of Internal MedicineKobe University Graduate School of MedicineHyogoJapan
| | - Atsushi Goto
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Taichi Shimazu
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Manami Inoue
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
- Graduate School of MedicineThe University of TokyoTokyoJapan
| | - Motoki Iwasaki
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
| | - Masaru Yoshida
- Division of GastroenterologyDepartment of Internal MedicineKobe University Graduate School of MedicineHyogoJapan
- Department of Internal RelatedMetabolomics ResearchKobe University Graduate School of MedicineHyogoJapan
- AMED‐CRESTAMEDHyogoJapan
| | - Shoichiro Tsugane
- Epidemiology and Prevention GroupCenter for Public Health SciencesNational Cancer CenterTokyoJapan
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A HILIC-UHPLC–MS/MS untargeted urinary metabonomics combined with quantitative analysis of five polar biomarkers on osteoporosis rats after oral administration of Gushudan. J Chromatogr B Analyt Technol Biomed Life Sci 2018; 1072:40-49. [DOI: 10.1016/j.jchromb.2017.10.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 09/30/2017] [Accepted: 10/04/2017] [Indexed: 01/03/2023]
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Lubes G, Goodarzi M. GC-MS based metabolomics used for the identification of cancer volatile organic compounds as biomarkers. J Pharm Biomed Anal 2017; 147:313-322. [PMID: 28750734 DOI: 10.1016/j.jpba.2017.07.013] [Citation(s) in RCA: 78] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2017] [Revised: 07/13/2017] [Accepted: 07/14/2017] [Indexed: 01/27/2023]
Abstract
A biomarker can be a metabolite, coming from a metabolic pathway or cell process, which might be employed in the diagnostic of diseases, predict patient response towards chemical therapies and/or monitor disease recurrences. Biomarkers, e.g. aldehydes or hydrocarbons, are often identified from different body fluids such as blood, urine, serum, saliva or from various tissues samples, and their concentration can vary from one sample to the other. However, the detection and the action of these biomarkers for diseases is a complicated process. Cancer is one of the main cause of death worldwide. The main characteristic of cancerous tumor is the uncontrolled growing of cells inside the organism. Likely, these uncontrolled growths are as consequence changes in the metabolism that could be analytically monitored. Depending on where the cancer cells are located, they provide different characteristics profiles. These profiles as fingerprints are used for differentiation in a comparison to normal cells. This critical study aimed at highlighting the latest progress in this area, especially in the employment of gas chromatography for the monitoring of volatile organic compounds (VOCs) and the identification of possible molecules used as biomarkers for cancer therapy.
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Affiliation(s)
- Giuseppe Lubes
- Laboratorio de Equilibrios en Solución, Universidad Simón Bolívar, Venezuela
| | - Mohammad Goodarzi
- Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States.
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