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Cao Y, Qin Y, Cheng Q, Zhong J, Han B, Li Y. Bifunctional nanomaterial enabled high-specific isolation of urinary exosomes for cervical cancer metabolomics analysis and biomarker discovery. Talanta 2025; 285:127280. [PMID: 39613490 DOI: 10.1016/j.talanta.2024.127280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 11/10/2024] [Accepted: 11/22/2024] [Indexed: 12/01/2024]
Abstract
Cervical cancer (CC) remains a critical public health issue, highlighting the importance of early detection. However, current methods such as cytological and HPV testing face challenges of invasiveness and low patient compliance. Exosomes, emerging as crucial in cancer diagnosis, offer promise due to their noninvasive, highly specificity, and abundant biomarkers. However, isolating exosomes efficiently remains challenging. In this study, we designed and synthesized a bifunctional affinity nanomaterial Fe3O4 @CD63-CLIKKPF, based on the synergistic interaction between its modified aptamer CD63 and peptide CLIKKPF, and CD63 protein and PS of exosomes which can achieve high specificity and high yield separation of urinary exosomes. Notably, the co-modified aptamer CD63 and peptide CLIKKPF not only enable efficient exosome isolation by leveraging dual-affinity mechanisms through a synergistic "AND" logic analysis, but also could be achieved on the Fe3O4 in one-step reaction at room temperature via Fe-S bonding. Combined with LC-MS/MS, we conducted exosome metabolomics analysis in healthy individuals and CC patients across various stages, and machine learning models demonstrated accurate classification (accuracy >0.822) and prediction capabilities for CC. Furthermore, six key metabolites indicative of CC progression were identified and validated in additional patient samples, highlighting their potential as biomarkers. Overall, this study establishes a novel method for exosome metabolomics in CC, offering insights for non-invasive early diagnosis and progression prediction on a large scale.
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Affiliation(s)
- Yiqing Cao
- Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, Shanghai, 201203, China
| | - Yulin Qin
- Department of Pharmacy, Minhang Hospital, Fudan University, Shanghai, 201100, China
| | - Qunxian Cheng
- Department of Gynecology and Obstetrics, Minhang Hospital, Fudan University, Shanghai, China
| | - Jialiang Zhong
- National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
| | - Bing Han
- Department of Pharmacy, Minhang Hospital, Fudan University, Shanghai, 201100, China.
| | - Yan Li
- Department of Pharmaceutical Analysis, School of Pharmacy, Fudan University, Shanghai, 201203, China; Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University, Shanghai, 201203, China; Innovative Center for New Drug Development of Immune Inflammatory Diseases, Fudan University, Shanghai, 201203, China.
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Xu X, Zeng C, Qing B, He Y, Song G, Wang J, Yu S, Zhang T, Wei Q, Liu L, Wen H, Hu J, Zhang W, Li Y, Chen Y, Xia Z. Development of a urine-based metabolomics approach for multi-cancer screening and tumor origin prediction. Front Immunol 2024; 15:1449103. [PMID: 39735533 PMCID: PMC11671364 DOI: 10.3389/fimmu.2024.1449103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Accepted: 11/27/2024] [Indexed: 12/31/2024] Open
Abstract
Background Cancer remains a leading cause of mortality worldwide. A non-invasive screening solution was required for early diagnosis of cancer. Multi-cancer early detection (MCED) tests have been considered to address the challenge by simultaneously identifying multiple types of cancer within a single test using minimally invasive blood samples. However, a multi-cancer screening strategy utilizing urine-based metabolomics has not yet been developed. Methods We enrolled 911 cancer patients with 548 lung cancer (LC), 177 with gastric cancer (GC), and 186 with colorectal cancer (CRC), alongside 563 individuals with non-cancerous benign diseases and 229 healthy controls (HC) and investigated the metabolic profiles of urine samples. Participants were randomly allocated to discovery and validation cohorts. The discovery cohort was used for identifying multi-cancer and tissue-specific signatures to build the cancer screening and tumor origin prediction models, while the validation cohort was employed for assessing the performance of these models. Results We identified and annotated a total of 360 metabolites from the urine samples. Using the LASSO regression algorithm, 18 metabolites were characterized as urinary metabolic biomarkers and exhibited excellent discriminative performance between cancer patients and HC with AUC of 0.96 in the validation cohort. In comparison with the performance of traditional tumor markers CEA, the screening model performed higher sensitivity across the cancer stages, with a particularly increase in sensitivity among early-stage cancer patients. Moreover, the screening model also exhibited in high classification of cancers from non-cancerous group, comprising with HC and benign disease participants. Furthermore, two non-overlapping metabolic panels were selected to differentiate LC from Non-LC and GC from CRC with the AUC values of 0.87 and 0.83 in validation cohorts, respectively. Additionally, the model accurately predicted the origin of three lethal cancers: lung, gastric, and colorectal, with an overall accuracy of 0.75. The AUC values for LC, GC, and CRC were 0.88, 0.88, and 0.80, respectively. Discussion Our study demonstrates the potential of urine-based metabolomics for multi-cancer early detection. The approach offers non-invasive cancer screening, promising widespread implementation in population-based programs for early detection and improved outcomes. Further validation and expansion are needed for broader clinical applicability.
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Affiliation(s)
- Xinping Xu
- Jiangxi Institute of Respiratory Disease, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Chunyan Zeng
- The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Bei Qing
- The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yun He
- Metanotitia Inc., Shenzhen, China
| | - Guodong Song
- The Second Hospital of Tianjin Medical University, Tianjin, China
| | | | - Shuqi Yu
- Metanotitia Inc., Shenzhen, China
| | | | | | - Li Liu
- Metanotitia Inc., Shenzhen, China
| | - He Wen
- Metanotitia Inc., Shenzhen, China
| | | | - Wei Zhang
- The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yan Li
- Metanotitia Inc., Shenzhen, China
| | - Youxiang Chen
- The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Zhenkun Xia
- The Second Xiangya Hospital of Central South University, Changsha, China
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Bhardwaj JK, Siwach A, Sachdeva SN. Metabolomics and cellular altered pathways in cancer biology: A review. J Biochem Mol Toxicol 2024; 38:e23807. [PMID: 39148273 DOI: 10.1002/jbt.23807] [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: 03/05/2024] [Revised: 07/16/2024] [Accepted: 08/01/2024] [Indexed: 08/17/2024]
Abstract
Cancer is a deadly disease that affects a cell's metabolism and surrounding tissues. Understanding the fundamental mechanisms of metabolic alterations in cancer cells would assist in developing cancer treatment targets and approaches. From this perspective, metabolomics is a great analytical tool to clarify the mechanisms of cancer therapy as well as a useful tool to investigate cancer from a distinct viewpoint. It is a powerful emerging technology that detects up to thousands of molecules in tissues and biofluids. Like other "-omics" technologies, metabolomics involves the comprehensive investigation of micromolecule metabolites and can reveal important details about the cancer state that is otherwise not apparent. Recent developments in metabolomics technologies have made it possible to investigate cancer metabolism in greater depth and comprehend how cancer cells utilize metabolic pathways to make the amino acids, nucleotides, and lipids required for tumorigenesis. These new technologies have made it possible to learn more about cancer metabolism. Here, we review the cellular and systemic effects of cancer and cancer treatments on metabolism. The current study provides an overview of metabolomics, emphasizing the current technologies and their use in clinical and translational research settings.
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Affiliation(s)
- Jitender Kumar Bhardwaj
- Reproductive Physiology Laboratory, Department of Zoology, Kurukshetra University, Kurukshetra, Haryana, India
| | - Anshu Siwach
- Reproductive Physiology Laboratory, Department of Zoology, Kurukshetra University, Kurukshetra, Haryana, India
| | - Som Nath Sachdeva
- Department of Civil Engineering, National Institute of Technology, Kurukshetra and Kurukshetra University, Kurukshetra, Haryana, India
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Bauer BA, Schmidt CM, Ruddy KJ, Olson JE, Meydan C, Schmidt JC, Smith SY, Couch FJ, Earls JC, Price ND, Dudley JT, Mason CE, Zhang B, Phipps SM, Schmidt MA. A Multiomics, Molecular Atlas of Breast Cancer Survivors. Metabolites 2024; 14:396. [PMID: 39057719 PMCID: PMC11279123 DOI: 10.3390/metabo14070396] [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: 06/02/2024] [Revised: 07/09/2024] [Accepted: 07/15/2024] [Indexed: 07/28/2024] Open
Abstract
Breast cancer imposes a significant burden globally. While the survival rate is steadily improving, much remains to be elucidated. This observational, single time point, multiomic study utilizing genomics, proteomics, targeted and untargeted metabolomics, and metagenomics in a breast cancer survivor (BCS) and age-matched healthy control cohort (N = 100) provides deep molecular phenotyping of breast cancer survivors. In this study, the BCS cohort had significantly higher polygenic risk scores for breast cancer than the control group. Carnitine and hexanoyl carnitine were significantly different. Several bile acid and fatty acid metabolites were significantly dissimilar, most notably the Omega-3 Index (O3I) (significantly lower in BCS). Proteomic and metagenomic analyses identified group and pathway differences, which warrant further investigation. The database built from this study contributes a wealth of data on breast cancer survivorship where there has been a paucity, affording the ability to identify patterns and novel insights that can drive new hypotheses and inform future research. Expansion of this database in the treatment-naïve, newly diagnosed, controlling for treatment confounders, and through the disease progression, can be leveraged to profile and contextualize breast cancer and breast cancer survivorship, potentially leading to the development of new strategies to combat this disease and improve the quality of life for its victims.
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Affiliation(s)
| | - Caleb M. Schmidt
- Sovaris Aerospace, Boulder, CO 80302, USA
- Advanced Pattern Analysis and Human Performance Group, Boulder, CO 80302, USA
| | | | | | - Cem Meydan
- Thorne Research, Inc., Summerville, SC 29483, USA
| | - Julian C. Schmidt
- Sovaris Aerospace, Boulder, CO 80302, USA
- Advanced Pattern Analysis and Human Performance Group, Boulder, CO 80302, USA
| | | | | | | | - Nathan D. Price
- Thorne Research, Inc., Summerville, SC 29483, USA
- Buck Institute for Research on Aging, Novato, CA 94945, USA
| | | | | | - Bodi Zhang
- Thorne Research, Inc., Summerville, SC 29483, USA
| | | | - Michael A. Schmidt
- Sovaris Aerospace, Boulder, CO 80302, USA
- Advanced Pattern Analysis and Human Performance Group, Boulder, CO 80302, USA
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Gadwal A, Panigrahi P, Khokhar M, Sharma V, Setia P, Vishnoi JR, Elhence P, Purohit P. A critical appraisal of the role of metabolomics in breast cancer research and diagnostics. Clin Chim Acta 2024; 561:119836. [PMID: 38944408 DOI: 10.1016/j.cca.2024.119836] [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: 03/30/2024] [Revised: 06/24/2024] [Accepted: 06/24/2024] [Indexed: 07/01/2024]
Abstract
Breast cancer (BC) remains the most prevalent cancer among women worldwide, despite significant advancements in its prevention and treatment. The escalating incidence of BC globally necessitates continued research into novel diagnostic and therapeutic strategies. Metabolomics, a burgeoning field, offers a comprehensive analysis of all metabolites within a cell, tissue, system, or organism, providing crucial insights into the dynamic changes occurring during cancer development and progression. This review focuses on the metabolic alterations associated with BC, highlighting the potential of metabolomics in identifying biomarkers for early detection, diagnosis, treatment and prognosis. Metabolomics studies have revealed distinct metabolic signatures in BC, including alterations in lipid metabolism, amino acid metabolism, and energy metabolism. These metabolic changes not only support the rapid proliferation of cancer cells but also influence the tumour microenvironment and therapeutic response. Furthermore, metabolomics holds great promise in personalized medicine, facilitating the development of tailored treatment strategies based on an individual's metabolic profile. By providing a holistic view of the metabolic changes in BC, metabolomics has the potential to revolutionize our understanding of the disease and improve patient outcomes.
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Affiliation(s)
- Ashita Gadwal
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Pragyan Panigrahi
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Manoj Khokhar
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Vaishali Sharma
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Puneet Setia
- Department of Forensic Medicine and Toxicology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Jeewan Ram Vishnoi
- Department of Oncosurgery, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India
| | - Poonam Elhence
- Department of Pathology, All India Institute of Medical Sciences, Jodhpur Rajasthan, 342005, India
| | - Purvi Purohit
- Department of Biochemistry, All India Institute of Medical Sciences, Jodhpur, Rajasthan, 342005, India.
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Jia Y, Zou K, Zou L. Research progress of metabolomics in cervical cancer. Eur J Med Res 2023; 28:586. [PMID: 38093395 PMCID: PMC10717910 DOI: 10.1186/s40001-023-01490-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 10/30/2023] [Indexed: 12/17/2023] Open
Abstract
INTRODUCTION Cervical cancer threatens women's health seriously. In recent years, the incidence of cervical cancer is on the rise, and the age of onset tends to be younger. Prevention, early diagnosis and specific treatment have become the main means to change the prognosis of cervical cancer patients. Metabolomics research can directly reflect the changes of biochemical processes and microenvironment in the body, which can provide a comprehensive understanding of the changes of metabolites in the process of disease occurrence and development, and provide new ways for the prevention and diagnosis of diseases. OBJECTIVES The aim of this study is to review the metabolic changes in cervical cancer and the application of metabolomics in the diagnosis and treatment. METHODS PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2022. RESULTS With the emergence of metabolomics, metabolic regulation and cancer research are further becoming a focus of attention. By directly reflecting the changes in the microenvironment of the body, metabolomics research can provide a comprehensive understanding of the patterns of metabolites in the occurrence and development of diseases, thus providing new ideas for disease prevention and diagnosis. CONCLUSION With the continuous, in-depth research on metabolomics research technology, it will bring more benefits in the screening, diagnosis and treatment of cervical cancer with its advantages of holistic and dynamic nature.
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Affiliation(s)
- Yuhan Jia
- Department of Radiotherapy, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, China
| | - Kun Zou
- Department of Radiotherapy, The First Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
| | - Lijuan Zou
- Department of Radiotherapy, The Second Hospital of Dalian Medical University, Dalian, Liaoning Province, China.
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Sequeira-Antunes B, Ferreira HA. Urinary Biomarkers and Point-of-Care Urinalysis Devices for Early Diagnosis and Management of Disease: A Review. Biomedicines 2023; 11:biomedicines11041051. [PMID: 37189669 DOI: 10.3390/biomedicines11041051] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2023] [Revised: 03/10/2023] [Accepted: 03/27/2023] [Indexed: 03/31/2023] Open
Abstract
Biosensing and microfluidics technologies are transforming diagnostic medicine by accurately detecting biomolecules in biological samples. Urine is a promising biological fluid for diagnostics due to its noninvasive collection and wide range of diagnostic biomarkers. Point-of-care urinalysis, which integrates biosensing and microfluidics, has the potential to bring affordable and rapid diagnostics into the home to continuing monitoring, but challenges still remain. As such, this review aims to provide an overview of biomarkers that are or could be used to diagnose and monitor diseases, including cancer, cardiovascular diseases, kidney diseases, and neurodegenerative disorders, such as Alzheimer’s disease. Additionally, the different materials and techniques for the fabrication of microfluidic structures along with the biosensing technologies often used to detect and quantify biological molecules and organisms are reviewed. Ultimately, this review discusses the current state of point-of-care urinalysis devices and highlights the potential of these technologies to improve patient outcomes. Traditional point-of-care urinalysis devices require the manual collection of urine, which may be unpleasant, cumbersome, or prone to errors. To overcome this issue, the toilet itself can be used as an alternative specimen collection and urinalysis device. This review then presents several smart toilet systems and incorporated sanitary devices for this purpose.
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Pan A, Truong TN, Su YH, Dao DY. Circulating Biomarkers for the Early Diagnosis and Management of Hepatocellular Carcinoma with Potential Application in Resource-Limited Settings. Diagnostics (Basel) 2023; 13:676. [PMID: 36832164 PMCID: PMC9954913 DOI: 10.3390/diagnostics13040676] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2022] [Revised: 02/02/2023] [Accepted: 02/07/2023] [Indexed: 02/15/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is among the world's third most lethal cancers. In resource-limited settings (RLS), up to 70% of HCCs are diagnosed with limited curative treatments at an advanced symptomatic stage. Even when HCC is detected early and resection surgery is offered, the post-operative recurrence rate after resection exceeds 70% in five years, of which about 50% occur within two years of surgery. There are no specific biomarkers addressing the surveillance of HCC recurrence due to the limited sensitivity of the available methods. The primary goal in the early diagnosis and management of HCC is to cure disease and improve survival, respectively. Circulating biomarkers can be used as screening, diagnostic, prognostic, and predictive biomarkers to achieve the primary goal of HCC. In this review, we highlighted key circulating blood- or urine-based HCC biomarkers and considered their potential applications in resource-limited settings, where the unmet medical needs of HCC are disproportionately highly significant.
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Affiliation(s)
- Annabelle Pan
- School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
| | - Thai N. Truong
- Department of Internal Medicine, Campus in Thanh Hoa, Hanoi Medical University, Thanh Hoa 40000, Vietnam
| | - Ying-Hsiu Su
- Department of Translational Medical Science, The Baruch S. Blumberg Institute, Doylestown, PA 18902, USA
| | - Doan Y Dao
- School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA
- Center of Excellence for Liver Disease in Vietnam, Johns Hopkins University of Medicine, Baltimore, MD 21205, USA
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Shekher A, Puneet, Awasthee N, Kumar U, Raj R, Kumar D, Gupta SC. Association of altered metabolic profiles and long non-coding RNAs expression with disease severity in breast cancer patients: analysis by 1H NMR spectroscopy and RT-q-PCR. Metabolomics 2023; 19:8. [PMID: 36710275 DOI: 10.1007/s11306-023-01972-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 01/12/2023] [Indexed: 01/31/2023]
Abstract
INTRODUCTION Globally, one of the major causes of cancer related deaths in women is breast cancer. Although metabolic pattern is altered in cancer patients, robust metabolic biomarkers with a potential to improve the screening and disease monitoring are lacking. A complete metabolome profiling of breast cancer patients may lead to the identification of diagnostic/prognostic markers and potential targets. OBJECTIVES The aim of this study was to analyze the metabolic profile in the serum from 43 breast cancer patients and 13 healthy individuals. MATERIALS & METHODS We used 1H NMR spectroscopy for the identification and quantification of metabolites. q-RT-PCR was used to examine the relative expression of lncRNAs. RESULTS Metabolites such as amino acids, lipids, membrane metabolites, lipoproteins, and energy metabolites were observed in the serum from both patients and healthy individuals. Using unsupervised PCA, supervised PLS-DA, supervised OPLS-DA, and random forest classification, we observed that more than 25 metabolites were altered in the breast cancer patients. Metabolites with AUC value > 0.9 were selected for further analysis that revealed significant elevation of lactate, LPR and glycerol, while the level of glucose, succinate, and isobutyrate was reduced in breast cancer patients in comparison to healthy control. The level of these metabolites (except LPR) was altered in advanced-stage breast cancer patients in comparison to early-stage breast cancer patients. The altered metabolites were also associated with over 25 signaling pathways related to metabolism. Further, lncRNAs such as H19, MEG3 and GAS5 were dysregulated in the breast tumor tissue in comparison to normal adjacent tissue. CONCLUSION The study provides insights into metabolic alteration in breast cancer patients. It also provides an avenue to examine the association of lncRNAs with metabolic patterns in patients.
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Affiliation(s)
- Anusmita Shekher
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
- Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
| | - Puneet
- Department of General Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
| | - Nikee Awasthee
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India
- Department of Anatomy and Cell Biology, College of Medicine, University of Florida, Gainesville, FL, 32610, USA
| | - Umesh Kumar
- Centre of Biomedical Research (CBMR), SGPGIMS, Lucknow, Uttar Pradesh, 226 014, India
| | - Ritu Raj
- Centre of Biomedical Research (CBMR), SGPGIMS, Lucknow, Uttar Pradesh, 226 014, India
| | - Dinesh Kumar
- Centre of Biomedical Research (CBMR), SGPGIMS, Lucknow, Uttar Pradesh, 226 014, India.
| | - Subash Chandra Gupta
- Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, 221 005, India.
- Department of Biochemistry, All India Institute of Medical Sciences, Guwahati, Assam, 781101, India.
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Khan H, Shah MR, Barek J, Malik MI. Cancer biomarkers and their biosensors: A comprehensive review. Trends Analyt Chem 2022. [DOI: 10.1016/j.trac.2022.116813] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
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Kaszak I, Witkowska-Piłaszewicz O, Domrazek K, Jurka P. The Novel Diagnostic Techniques and Biomarkers of Canine Mammary Tumors. Vet Sci 2022; 9:526. [PMID: 36288138 PMCID: PMC9610006 DOI: 10.3390/vetsci9100526] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/12/2022] [Accepted: 09/22/2022] [Indexed: 07/25/2023] Open
Abstract
Canine mammary tumors (CMTs) are considered a serious clinical problem in older bitches. Due to the high malignancy rate and poor prognosis, an early diagnosis is essential. This article is a summary of novel diagnostic techniques as well as the main biomarkers of CMTs. So far, CMTs are detected only when changes in mammary glands are clinically visible and surgical removal of the mass is the only recommended treatment. Proper diagnostics of CMT is especially important as they represent a very diverse group of tumors and therefore different treatment approaches may be required. Recently, new diagnostic options appeared, like a new cytological grading system of CMTs or B-mode ultrasound, the Doppler technique, contrast-enhanced ultrasound, and real-time elastography, which may be useful in pre-surgical evaluation. However, in order to detect malignancies before macroscopic changes are visible, evaluation of serum and tissue biomarkers should be considered. Among them, we distinguish markers of the cell cycle, proliferation, apoptosis, metastatic potential and prognosis, hormone receptors, inflammatory and more recent: metabolomic, gene expression, miRNA, and transcriptome sequencing markers. The use of a couple of the above-mentioned markers together seems to be the most useful for the early diagnosis of neoplastic diseases as well as to evaluate response to treatment, presence of tumor progression, or further prognosis. Molecular aspects of tumors seem to be crucial for proper understanding of tumorigenesis and the application of individual treatment options.
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Affiliation(s)
- Ilona Kaszak
- Laboratory of Small Animal Reproduction, Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland
| | - Olga Witkowska-Piłaszewicz
- Department of Pathology and Veterinary Diagnostics, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland
| | - Kinga Domrazek
- Laboratory of Small Animal Reproduction, Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland
| | - Piotr Jurka
- Laboratory of Small Animal Reproduction, Department of Small Animal Diseases and Clinic, Institute of Veterinary Medicine, Warsaw University of Life Sciences, 02-787 Warsaw, Poland
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Dehghani F, Yousefinejad S, Walker DI, Omidi F. Metabolomics for exposure assessment and toxicity effects of occupational pollutants: current status and future perspectives. Metabolomics 2022; 18:73. [PMID: 36083566 DOI: 10.1007/s11306-022-01930-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 08/19/2022] [Indexed: 11/24/2022]
Abstract
INTRODUCTION Work-related exposures to harmful agents or factors are associated with an increase in incidence of occupational diseases. These exposures often represent a complex mixture of different stressors, challenging the ability to delineate the mechanisms and risk factors underlying exposure-disease relationships. The use of omics measurement approaches that enable characterization of biological marker patterns provide internal indicators of molecular alterations, which could be used to identify bioeffects following exposure to a toxicant. Metabolomics is the comprehensive analysis of small molecule present in biological samples, and allows identification of potential modes of action and altered pathways by systematic measurement of metabolites. OBJECTIVES The aim of this study is to review the application of metabolomics studies for use in occupational health, with a focus on applying metabolomics for exposure monitoring and its relationship to occupational diseases. METHODS PubMed, Web of Science, Embase and Scopus electronic databases were systematically searched for relevant studies published up to 2021. RESULTS Most of reviewed studies included worker populations exposed to heavy metals such as As, Cd, Pb, Cr, Ni, Mn and organic compounds such as tetrachlorodibenzo-p-dioxin, trichloroethylene, polyfluoroalkyl, acrylamide, polyvinyl chloride. Occupational exposures were associated with changes in metabolites and pathways, and provided novel insight into the relationship between exposure and disease outcomes. The reviewed studies demonstrate that metabolomics provides a powerful ability to identify metabolic phenotypes and bioeffect of occupational exposures. CONCLUSION Continued application to worker populations has the potential to enable characterization of thousands of chemical signals in biological samples, which could lead to discovery of new biomarkers of exposure for chemicals, identify possible toxicological mechanisms, and improved understanding of biological effects increasing disease risk associated with occupational exposure.
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Affiliation(s)
- Fatemeh Dehghani
- Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran
- Research Center for Health Sciences, Research Institute for Health, Department of Occupational Health and Safety Engineering, School of Health Shiraz, University of Medical Sciences, Shiraz, Iran
| | - Saeed Yousefinejad
- Research Center for Health Sciences, Research Institute for Health, Department of Occupational Health and Safety Engineering, School of Health Shiraz, University of Medical Sciences, Shiraz, Iran.
| | - Douglas I Walker
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA
| | - Fariborz Omidi
- Research Center for Environmental Determinants of Health (RCEDH), Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Optimization and normalization strategies for long term untargeted HILIC-LC-qTOF-MS based metabolomics analysis: Early diagnosis of breast cancer. Microchem J 2022. [DOI: 10.1016/j.microc.2022.107658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Starodubtseva NL, Chagovets VV, Nekrasova ME, Nazarova NM, Tokareva AO, Bourmenskaya OV, Attoeva DI, Kukaev EN, Trofimov DY, Frankevich VE, Sukhikh GT. Shotgun Lipidomics for Differential Diagnosis of HPV-Associated Cervix Transformation. Metabolites 2022; 12:metabo12060503. [PMID: 35736434 PMCID: PMC9229224 DOI: 10.3390/metabo12060503] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/25/2022] [Accepted: 05/25/2022] [Indexed: 12/12/2022] Open
Abstract
A dramatic increase in cervical diseases associated with human papillomaviruses (HPV) in women of reproductive age has been observed over the past decades. An accurate differential diagnosis of the severity of cervical intraepithelial neoplasia and the choice of the optimal treatment requires the search for effective biomarkers with high diagnostic and prognostic value. The objective of this study was to introduce a method for rapid shotgun lipidomics to differentiate stages of HPV-associated cervix epithelium transformation. Tissue samples from 110 HPV-positive women with cervicitis (n = 30), low-grade squamous intraepithelial lesions (LSIL) (n = 30), high-grade squamous intraepithelial lesions (HSIL) (n = 30), and cervical cancers (n = 20) were obtained. The cervical epithelial tissue lipidome at different stages of cervix neoplastic transformation was studied by a shotgun label-free approach. It is based on electrospray ionization mass spectrometry (ESI-MS) data of a tissue extract. Lipidomic data were processed by the orthogonal projections to latent structures discriminant analysis (OPLS-DA) to build statistical models, differentiating stages of cervix transformation. Significant differences in the lipid profile between the lesion and surrounding tissues were revealed in chronic cervicitis, LSIL, HSIL, and cervical cancer. The lipids specific for HPV-induced cervical transformation mainly belong to glycerophospholipids: phosphatidylcholines, and phosphatidylethanolamines. The developed diagnostic OPLS-DA models were based on 23 marker lipids. More than 90% of these marker lipids positively correlated with the degree of cervix transformation. The algorithm was developed for the management of patients with HPV-associated diseases of the cervix, based on the panel of 23 lipids as a result. ESI-MS analysis of a lipid extract by direct injection through a loop, takes about 25 min (including preparation of the lipid extract), which is significantly less than the time required for the HPV test (several hours for hybrid capture and about an hour for PCR). This makes lipid mass spectrometric analysis a promising method for express diagnostics of HPV-associated neoplastic diseases of the cervix.
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Affiliation(s)
- Natalia L. Starodubtseva
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
- Moscow Institute of Physics and Technology, 141700 Moscow, Russia
| | - Vitaliy V. Chagovets
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
- Correspondence:
| | - Maria E. Nekrasova
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
| | - Niso M. Nazarova
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
| | - Alisa O. Tokareva
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
- V.L. Talrose Institute for Energy Problems of Chemical Physics, Russia Academy of Sciences, 119991 Moscow, Russia
| | - Olga V. Bourmenskaya
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
| | - Djamilja I. Attoeva
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
| | - Eugenii N. Kukaev
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
- Moscow Institute of Physics and Technology, 141700 Moscow, Russia
- V.L. Talrose Institute for Energy Problems of Chemical Physics, Russia Academy of Sciences, 119991 Moscow, Russia
| | - Dmitriy Y. Trofimov
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
| | - Vladimir E. Frankevich
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
| | - Gennady T. Sukhikh
- National Medical Research Center for Obstetrics Gynecology and Perinatology Named after Academician V.I., Kulakov of the Ministry of Healthcare of Russian Federation, 117997 Moscow, Russia; (N.L.S.); (M.E.N.); (N.M.N.); (A.O.T.); (O.V.B.); (D.I.A.); (E.N.K.); (D.Y.T.); (V.E.F.); (G.T.S.)
- Department of Obstetrics, Gynecology, Perinatology and Reproductology, First Moscow State Medical University Named after I.M. Sechenov, 119991 Moscow, Russia
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15
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Breast cancer in the era of integrating “Omics” approaches. Oncogenesis 2022; 11:17. [PMID: 35422484 PMCID: PMC9010455 DOI: 10.1038/s41389-022-00393-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 03/27/2022] [Accepted: 03/30/2022] [Indexed: 12/24/2022] Open
Abstract
Worldwide, breast cancer is the leading cause of cancer-related deaths in women. Breast cancer is a heterogeneous disease characterized by different clinical outcomes in terms of pathological features, response to therapies, and long-term patient survival. Thus, the heterogeneity found in this cancer led to the concept that breast cancer is not a single disease, being very heterogeneous both at the molecular and clinical level, and rather represents a group of distinct neoplastic diseases of the breast and its cells. Indubitably, in the past decades we witnessed a significant development of innovative therapeutic approaches, including targeted and immunotherapies, leading to impressive results in terms of increased survival for breast cancer patients. However, these multimodal treatments fail to prevent recurrence and metastasis. Therefore, it is urgent to improve our understanding of breast tumor and metastasis biology. Over the past few years, high-throughput “omics” technologies through the identification of novel biomarkers and molecular profiling have shown their great potential in generating new insights in the study of breast cancer, also improving diagnosis, prognosis and prediction of response to treatment. In this review, we discuss how the implementation of “omics” strategies and their integration may lead to a better comprehension of the mechanisms underlying breast cancer. In particular, with the aim to investigate the correlation between different “omics” datasets and to define the new important key pathway and upstream regulators in breast cancer, we applied a new integrative meta-analysis method to combine the results obtained from genomics, proteomics and metabolomics approaches in different revised studies.
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16
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Özer Ö, Nemutlu E, Reçber T, Eylem CC, Aktas BY, Kır S, Kars A, Aksoy S. Liquid biopsy markers for early diagnosis of brain metastasis patients with breast cancer by metabolomics. EUROPEAN JOURNAL OF MASS SPECTROMETRY (CHICHESTER, ENGLAND) 2022; 28:56-64. [PMID: 35422172 DOI: 10.1177/14690667221093871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Introduction: Breast cancer is the most common cancer in women and is the second most common cause of cancer related mortality. Metabolomics, the identification of small metabolites, is a technique for determining the amount of these metabolites. Objectives: This study aimed to identify markers for the early diagnosis of brain metastasis by metabolomic methods in breast cancer patients. Methods: A total of 88 breast cancer patients with distant metastases were included in the study. The patients were divided into two groups according to their metastasis status: patients with brain metastases and distant metastases without any brain metastases. Liquid chromatography quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) and gas chromatography-mass spectrometry (GC-MS) analysis methods were used for metabolomic analyses. Results: 33 of them, 88 patients had brain metastasis, and 55 patients had distant metastases without brain metastasis. A total of 72 and 35 metabolites were identified by the GC-MS and LC-qTOF-MS analysis, respectively. 47 of them were found to be significantly different in patients with brain metastasis. The pathway analysis, performed with significantly altered metabolites, showed that aminoacyl tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, alanine, aspartate, and glutamate metabolism, arginine biosynthesis, glycine, serine, and threonine metabolism pathways significantly altered in patients with brain metastasis. Predictive accuracies for have identifying the brain metastasis were performed with receiver operating characteristic (ROC) analysis, and the model with fifteen metabolites has 96.9% accuracy. Conclusions: While these results should be supported by prospective studies, these data are promising for early detection of brain metastasis with markers in liquid biopsy samples.
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Affiliation(s)
- Özge Özer
- Department of Internal Medicine, Hacettepe University School of Medicine, Ankara, Turkey
| | - Emirhan Nemutlu
- Faculty of Pharmacy, Department of Analytical Chemistry, 37515Hacettepe University, Ankara, Turkey
| | - Tuba Reçber
- Faculty of Pharmacy, Department of Analytical Chemistry, 37515Hacettepe University, Ankara, Turkey
| | - Cemil Can Eylem
- Faculty of Pharmacy, Department of Analytical Chemistry, 37515Hacettepe University, Ankara, Turkey
| | - Burak Yasin Aktas
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
| | - Sedef Kır
- Faculty of Pharmacy, Department of Analytical Chemistry, 37515Hacettepe University, Ankara, Turkey
| | - Ayse Kars
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
| | - Sercan Aksoy
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Turkey
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17
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Owens GL, Barr CE, White H, Njoku K, Crosbie EJ. OUP accepted manuscript. Carcinogenesis 2022; 43:311-320. [PMID: 35166350 PMCID: PMC9118979 DOI: 10.1093/carcin/bgac016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/06/2021] [Accepted: 02/12/2022] [Indexed: 11/12/2022] Open
Abstract
Currently, the only definitive method for diagnosing ovarian cancer involves histological examination of tissue obtained at time of surgery or by invasive biopsy. Blood has traditionally been the biofluid of choice in ovarian cancer biomarker discovery; however, there has been a growing interest in exploring urinary biomarkers, particularly as it is non-invasive. In this systematic review, we present the diagnostic accuracy of urinary biomarker candidates for the detection of ovarian cancer. A comprehensive literature search was performed using the MEDLINE/PubMed and EMBASE, up to 1 April 2021. All included studies reported the diagnostic accuracy using sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. Risk of bias and applicability of included studies were assessed using the QUADAS-2 tool. Twenty-seven studies were included in the narrative synthesis. Protein/peptide biomarkers were most commonly described (n = 18), with seven studies reporting composite scores of multiple protein-based targets. The most frequently described urinary protein biomarker was HE4 (n = 5), with three studies reporting a sensitivity and specificity > 80%. Epigenetic (n = 1) and metabolomic/organic compound biomarkers (n = 8) were less commonly described. Overall, six studies achieved a sensitivity and specificity of >90% and/or an AUC > 0.9. Evaluation of urinary biomarkers for the detection of ovarian cancer is a dynamic and growing field. Currently, the most promising biomarkers are those that interrogate metabolomic pathways and organic compounds, or quantify multiple proteins. Such biomarkers require external validation in large, prospective observational studies before they can be implemented into clinical practice.
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Affiliation(s)
- Gemma L Owens
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK
- Obstetrics and Gynaecology Department, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
- To whom correspondence should be addressed. Tel: 0161 276 6461;
| | - Chloe E Barr
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK
- Obstetrics and Gynaecology Department, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
| | - Holly White
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK
- Obstetrics and Gynaecology Department, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
| | - Kelechi Njoku
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK
- Obstetrics and Gynaecology Department, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
| | - Emma J Crosbie
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary’s Hospital, Manchester M13 9WL, UK
- Obstetrics and Gynaecology Department, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WL, UK
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18
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Gouzerh F, Bessière JM, Ujvari B, Thomas F, Dujon AM, Dormont L. Odors and cancer: Current status and future directions. Biochim Biophys Acta Rev Cancer 2021; 1877:188644. [PMID: 34737023 DOI: 10.1016/j.bbcan.2021.188644] [Citation(s) in RCA: 23] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/22/2021] [Accepted: 10/23/2021] [Indexed: 02/07/2023]
Abstract
Cancer is the second leading cause of death in the world. Because tumors detected at early stages are easier to treat, the search for biomarkers-especially non-invasive ones-that allow early detection of malignancies remains a central goal to reduce cancer mortality. Cancer, like other pathologies, often alters body odors, and much has been done by scientists over the last few decades to assess the value of volatile organic compounds (VOCs) as signatures of cancers. We present here a quantitative review of 208 studies carried out between 1984 and 2020 that explore VOCs as potential biomarkers of cancers. We analyzed the main findings of these studies, listing and classifying VOCs related to different cancer types while considering both sampling methods and analysis techniques. Considering this synthesis, we discuss several of the challenges and the most promising prospects of this research direction in the war against cancer.
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Affiliation(s)
- Flora Gouzerh
- CREEC/CANECEV (CREES), Montpellier, France; MIVEGEC, Université de Montpellier, CNRS, IRD, Montpellier, France; CEFE, Univ Montpellier, CNRS, EPHE, IRD, Univ Paul Valéry Montpellier 3, Montpellier, France.
| | - Jean-Marie Bessière
- Ecole Nationale de Chimie de Montpellier, Laboratoire de Chimie Appliquée, Montpellier, France
| | - Beata Ujvari
- Deakin University, School of Life and Environmental Sciences, Centre for Integrative Ecology, Waurn Ponds, Vic 3216, Australia
| | - Frédéric Thomas
- CREEC/CANECEV (CREES), Montpellier, France; MIVEGEC, Université de Montpellier, CNRS, IRD, Montpellier, France
| | - Antoine M Dujon
- CREEC/CANECEV (CREES), Montpellier, France; MIVEGEC, Université de Montpellier, CNRS, IRD, Montpellier, France; Deakin University, School of Life and Environmental Sciences, Centre for Integrative Ecology, Waurn Ponds, Vic 3216, Australia
| | - Laurent Dormont
- CEFE, Univ Montpellier, CNRS, EPHE, IRD, Univ Paul Valéry Montpellier 3, Montpellier, France
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19
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Chen J, Chen Y, Sun K, Wang Y, He H, Sun L, Ha S, Li X, Ou Y, Zhang X, Bi Y. Prediction of Ovarian Cancer-Related Metabolites Based on Graph Neural Network. Front Cell Dev Biol 2021; 9:753221. [PMID: 34676219 PMCID: PMC8525679 DOI: 10.3389/fcell.2021.753221] [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: 08/04/2021] [Accepted: 08/27/2021] [Indexed: 11/13/2022] Open
Abstract
Ovarian cancer is one of the three most malignant tumors of the female reproductive system. At present, researchers do not know its pathogenesis, which makes the treatment effect unsatisfactory. Metabolomics is closely related to drug efficacy, safety evaluation, mechanism of action, and rational drug use. Therefore, identifying ovarian cancer-related metabolites could greatly help researchers understand the pathogenesis and develop treatment plans. However, the measurement of metabolites is inaccurate and greatly affects the environment, and biological experiment is time-consuming and costly. Therefore, researchers tend to use computational methods to identify disease-related metabolites in large scale. Since the hypothesis that similar diseases are related to similar metabolites is widely accepted, in this paper, we built both disease similarity network and metabolite similarity network and used graph convolutional network (GCN) to encode these networks. Then, support vector machine (SVM) was used to identify whether a metabolite is related to ovarian cancer. The experiment results show that the AUC and AUPR of our method are 0.92 and 0.81, respectively. Finally, we proposed an effective method to prioritize ovarian cancer-related metabolites in large scale.
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Affiliation(s)
- Jingjing Chen
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yingying Chen
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Kefeng Sun
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yu Wang
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Hui He
- Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
| | - Lin Sun
- Department of Reproductive Medicine, Dalian Maternal and Children's Centre, Dalian, China
| | - Sifu Ha
- Department of Reproductive Medicine, Dalian Maternal and Children's Centre, Dalian, China
| | - Xiaoxiao Li
- Graduate School of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Yifei Ou
- Graduate School of Heilongjiang University of Chinese Medicine, Harbin, China
| | - Xue Zhang
- Department of General Practice, Beijing Friendship Hospital, Capital Medical University, Beijing, China
| | - Yanli Bi
- Department of Reproductive Medicine, The First Affiliated Hospital, Henan University of Chinese Medicine, Zhengzhou, China
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20
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Amalric A, Bastide A, Attina A, Choquet A, Vialaret J, Lehmann S, David A, Hirtz C. Quantifying RNA modifications by mass spectrometry: a novel source of biomarkers in oncology. Crit Rev Clin Lab Sci 2021; 59:1-18. [PMID: 34473579 DOI: 10.1080/10408363.2021.1958743] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Despite significant progress in targeted therapies, cancer recurrence remains a major cause of mortality worldwide. Identification of accurate biomarkers, through molecular profiling in healthy and cancer patient samples, will improve diagnosis and promote personalized medicine. While genetic and epigenetic alterations of DNA are currently exploited as cancer biomarkers, their robustness is limited by tumor heterogeneity. Recently, cancer-associated changes in RNA marks have emerged as a promising source of diagnostic and prognostic biomarkers. RNA epigenetics (also known as epitranscriptomics) is an emerging field in which at least 150 chemical modifications in all types of RNA (mRNA, tRNA, lncRNA, rRNA, and microRNA) have been detected. These modifications fine-tune gene expression in both physiological and pathological processes. A growing number of studies have established links between specific modified nucleoside levels in solid/liquid biopsies, and cancer onset and progression. In this review, we highlight the potential role of epitranscriptomic markers in refining cancer diagnosis and/or prognosis. RNA modification patterns may contain important information for establishing an initial diagnosis, monitoring disease evolution, and predicting response to treatment. Furthermore, recent developments in mass spectrometry allow reliable quantification of RNA marks in solid biopsies and biological fluids. We discuss the great potential of mass spectrometry for identifying epitranscriptomic biomarker signatures in cancer diagnosis. While there are various methods to quantify modified nucleosides, most are unable to detect and quantify more than one type of RNA modification at a time. Mass spectrometry analyses, especially GC-MS/MS and LC-MS/MS, overcome this limitation and simultaneously detect modified nucleosides by multiple reaction monitoring. Indeed, several groups are currently validating mass spectrometry methods that quantify several nucleosides at one time in liquid biopsies. The challenge now is to exploit these powerful analytical tools to establish epitranscriptomic signatures that should open new perspectives in personalized medicine. This review summarizes the growing clinical field of analysis of RNA modifications and discusses pre-analytical and analytical approaches, focusing in particular on the development of new mass spectrometry tools and their clinical applications.
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Affiliation(s)
- Amandine Amalric
- IGF, University of Montpellier, CNRS, INSERM, Montpellier, France.,University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France
| | - Amandine Bastide
- IGF, University of Montpellier, CNRS, INSERM, Montpellier, France
| | - Aurore Attina
- University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France
| | - Armelle Choquet
- IGF, University of Montpellier, CNRS, INSERM, Montpellier, France
| | - Jerome Vialaret
- University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France
| | - Sylvain Lehmann
- University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France
| | - Alexandre David
- IGF, University of Montpellier, CNRS, INSERM, Montpellier, France.,University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France
| | - Christophe Hirtz
- University of Montpellier, IRMB-PPC, INM, CHU Montpellier, INSERM CNRS, Montpellier, France
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21
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De Matteis S, Bonafè M, Giudetti AM. Urinary Metabolic Biomarkers in Cancer Patients: An Overview. Methods Mol Biol 2021; 2292:203-212. [PMID: 33651364 DOI: 10.1007/978-1-0716-1354-2_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/16/2023]
Abstract
The pathogenesis of cancer involves multiple molecular alterations at the level of genome, epigenome, and stromal environment, resulting in several deregulated signal transduction pathways. Metabolites are not only end products of gene and protein expression but also a consequence of the mutual relationship between the genome and the internal environment. Considering that metabolites serve as a comprehensive chemical fingerprint of cell metabolism, metabolomics is emerging as the method able to discover metabolite biomarkers that can be developed for early cancer detection, prognosis, and response to treatment. Urine represents a noninvasive source, available and rich in metabolites, useful for cancer diagnosis, prognosis, and treatment monitoring. In this chapter, we reported the main published evidences on urinary metabolic biomarkers in the studied cancers related to hepatopancreatic and urinary tract with the aim at discussing their promising role in clinical practice.
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Affiliation(s)
- Serena De Matteis
- Department of Medicine, Section of Oncology, University of Verona, Verona, Italy.
| | - Massimiliano Bonafè
- Department of Experimental, Diagnostic and Specialty Medicine, AlmaMater Studiorum, University of Bologna, Bologna, Italy
| | - Anna Maria Giudetti
- Department of Biological and Environmental Sciences and Technologies, University of Salento, Lecce, Italy
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22
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Bustamam MSA, Pantami HA, Azizan A, Shaari K, Min CC, Abas F, Nagao N, Maulidiani M, Banerjee S, Sulaiman F, Ismail IS. Complementary Analytical Platforms of NMR Spectroscopy and LCMS Analysis in the Metabolite Profiling of Isochrysis galbana. Mar Drugs 2021; 19:md19030139. [PMID: 33801258 PMCID: PMC7998644 DOI: 10.3390/md19030139] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 02/25/2021] [Accepted: 02/26/2021] [Indexed: 12/24/2022] Open
Abstract
This study was designed to profile the metabolites of Isochrysis galbana, an indigenous and less explored microalgae species. 1H Nuclear Magnetic Resonance (NMR) spectroscopy and Liquid Chromatography-Mass Spectrometry (LCMS) were used to establish the metabolite profiles of five different extracts of this microalga, which are hexane (Hex), ethyl acetate (EtOAc), absolute ethanol (EtOH), EtOH:water 1:1 (AqE), and 100% water (Aq). Partial least square discriminant analysis (PLS–DA) of the generated profiles revealed that EtOAc and Aq extracts contain a diverse range of metabolites as compared to the other extracts with a total of twenty-one metabolites, comprising carotenoids, polyunsaturated fatty acids, and amino acids, that were putatively identified from the NMR spectra. Meanwhile, thirty-two metabolites were successfully annotated from the LCMS/MS data, ten of which (palmitic acid, oleic acid, α-linolenic acid, arachidic acid, cholesterol, DHA, DPA, fucoxanthin, astaxanthin, and pheophytin) were similar to those present in the NMR profile. Another eleven glycerophospholipids were discovered using MS/MS-based molecular network (MN) platform. The results of this study, besides providing a better understanding of I.galbana’s chemical make-up, will be of importance in exploring this species potential as a feed ingredient in the aquaculture industry.
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Affiliation(s)
- Muhammad Safwan Ahamad Bustamam
- Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (M.S.A.B.); (A.A.); (K.S.); (F.A.); (S.B.); (F.S.)
| | - Hamza Ahmed Pantami
- Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia;
| | - Awanis Azizan
- Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (M.S.A.B.); (A.A.); (K.S.); (F.A.); (S.B.); (F.S.)
| | - Khozirah Shaari
- Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (M.S.A.B.); (A.A.); (K.S.); (F.A.); (S.B.); (F.S.)
- Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia;
| | - Chong Chou Min
- Department of Aquaculture, Faculty of Agriculture, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (C.C.M.); (N.N.)
| | - Faridah Abas
- Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (M.S.A.B.); (A.A.); (K.S.); (F.A.); (S.B.); (F.S.)
| | - Norio Nagao
- Department of Aquaculture, Faculty of Agriculture, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (C.C.M.); (N.N.)
| | - Maulidiani Maulidiani
- Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Kuala Nerus 21030, Terengganu, Malaysia;
| | - Sanjoy Banerjee
- Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (M.S.A.B.); (A.A.); (K.S.); (F.A.); (S.B.); (F.S.)
| | - Fadzil Sulaiman
- Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (M.S.A.B.); (A.A.); (K.S.); (F.A.); (S.B.); (F.S.)
| | - Intan Safinar Ismail
- Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia; (M.S.A.B.); (A.A.); (K.S.); (F.A.); (S.B.); (F.S.)
- Department of Chemistry, Faculty of Science, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia;
- Correspondence: ; Tel.: +60-3-9769-7492
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Sabtu SN, Sani SFA, Looi LM, Chiew SF, Pathmanathan D, Bradley DA, Osman Z. Indication of high lipid content in epithelial-mesenchymal transitions of breast tissues. Sci Rep 2021; 11:3250. [PMID: 33547362 PMCID: PMC7864999 DOI: 10.1038/s41598-021-81426-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Accepted: 12/21/2020] [Indexed: 02/06/2023] Open
Abstract
The epithelial-mesenchymal transition (EMT) is a crucial process in cancer progression and metastasis. Study of metabolic changes during the EMT process is important in seeking to understand the biochemical changes associated with cancer progression, not least in scoping for therapeutic strategies aimed at targeting EMT. Due to the potential for high sensitivity and specificity, Raman spectroscopy was used here to study the metabolic changes associated with EMT in human breast cancer tissue. For Raman spectroscopy measurements, tissue from 23 patients were collected, comprising non-lesional, EMT and non-EMT formalin-fixed and paraffin embedded breast cancer samples. Analysis was made in the fingerprint Raman spectra region (600-1800 cm-1) best associated with cancer progression biochemical changes in lipid, protein and nucleic acids. The ANOVA test followed by the Tukey's multiple comparisons test were conducted to see if there existed differences between non-lesional, EMT and non-EMT breast tissue for Raman spectroscopy measurements. Results revealed that significant differences were evident in terms of intensity between the non-lesional and EMT samples, as well as the EMT and non-EMT samples. Multivariate analysis involving independent component analysis, Principal component analysis and non-negative least square were used to analyse the Raman spectra data. The results show significant differences between EMT and non-EMT cancers in lipid, protein, and nucleic acids. This study demonstrated the capability of Raman spectroscopy supported by multivariate analysis in analysing metabolic changes in EMT breast cancer tissue.
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Affiliation(s)
- Siti Norbaini Sabtu
- Department of Physics, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - S F Abdul Sani
- Department of Physics, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia.
| | - L M Looi
- Department of Pathology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - S F Chiew
- Department of Pathology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - Dharini Pathmanathan
- Institute of Mathematical Sciences, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
| | - D A Bradley
- Centre for Biomedical Physics, Sunway University, Jalan Universiti, 46150, Petaling Jaya, Malaysia
- Department of Physics, University of Surrey, Guildford, GU2 7XH, UK
| | - Z Osman
- Department of Physics, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia
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Khamis MM, Adamko DJ, El-Aneed A. STRATEGIES AND CHALLENGES IN METHOD DEVELOPMENT AND VALIDATION FOR THE ABSOLUTE QUANTIFICATION OF ENDOGENOUS BIOMARKER METABOLITES USING LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY. MASS SPECTROMETRY REVIEWS 2021; 40:31-52. [PMID: 31617245 DOI: 10.1002/mas.21607] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Accepted: 09/08/2019] [Indexed: 06/10/2023]
Abstract
Metabolomics is a dynamically evolving field, with a major application in identifying biomarkers for drug development and personalized medicine. Numerous metabolomic studies have identified endogenous metabolites that, in principle, are eligible for translation to clinical practice. However, few metabolomic-derived biomarker candidates have been qualified by regulatory bodies for clinical applications. Such interruption in the biomarker qualification process can be largely attributed to various reasons including inappropriate study design and inadequate data to support the clinical utility of the biomarkers. In addition, the lack of robust assays for the routine quantification of candidate biomarkers has been suggested as a potential bottleneck in the biomarker qualification process. In fact, the nature of the endogenous metabolites precludes the application of the current validation guidelines for bioanalytical methods. As a result, there have been individual efforts in modifying existing guidelines and/or developing alternative approaches to facilitate method validation. In this review, three main challenges for method development and validation for endogenous metabolites are discussed, namely matrix effects evaluation, alternative analyte-free matrices, and the choice of internal standards (ISs). Some studies have modified the equations described by the European Medicines Agency for the evaluation of matrix effects. However, alternative strategies were also described; for instance, calibration curves can be generated in solvents and in biological samples and the slopes can be compared through ratios, relative standard deviation, or a modified Stufour suggested approaches while quantifying mainly endogenous metabolitesdent t-test. ISs, on the contrary, are diverse; in which seven different possible types, used in metabolomics-based studies, were identified in the literature. Each type has its advantages and limitations; however, isotope-labeled ISs and ISs created through isotope derivatization show superior performance. Finally, alternative matrices have been described and tested during method development and validation for the quantification of endogenous entities. These alternatives are discussed in detail, highlighting their advantages and shortcomings. The goal of this review is to compare, apprise, and debate current knowledge and practices in order to aid researchers and clinical scientists in developing robust assays needed during the qualification process of candidate metabolite biomarkers. © 2019 John Wiley & Sons Ltd. Mass Spec Rev.
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Affiliation(s)
- Mona M Khamis
- College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Rd, Saskatoon, Saskatchewan, S7N 5E5, Canada
| | - Darryl J Adamko
- Department of Pediatrics, College of Medicine, University of Saskatchewan, 103 Hospital Drive, Saskatoon, Saskatchewan, Canada
| | - Anas El-Aneed
- College of Pharmacy and Nutrition, University of Saskatchewan, 107 Wiggins Rd, Saskatoon, Saskatchewan, S7N 5E5, Canada
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25
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Tokarz J, Adamski J, Lanišnik Rižner T. Metabolomics for Diagnosis and Prognosis of Uterine Diseases? A Systematic Review. J Pers Med 2020; 10:294. [PMID: 33371433 PMCID: PMC7767462 DOI: 10.3390/jpm10040294] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 12/08/2020] [Accepted: 12/18/2020] [Indexed: 12/24/2022] Open
Abstract
This systematic review analyses the contribution of metabolomics to the identification of diagnostic and prognostic biomarkers for uterine diseases. These diseases are diagnosed invasively, which entails delayed treatment and a worse clinical outcome. New options for diagnosis and prognosis are needed. PubMed, OVID, and Scopus were searched for research papers on metabolomics in physiological fluids and tissues from patients with uterine diseases. The search identified 484 records. Based on inclusion and exclusion criteria, 44 studies were included into the review. Relevant data were extracted following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) checklist and quality was assessed using the QUADOMICS tool. The selected metabolomics studies analysed plasma, serum, urine, peritoneal, endometrial, and cervico-vaginal fluid, ectopic/eutopic endometrium, and cervical tissue. In endometriosis, diagnostic models discriminated patients from healthy and infertile controls. In cervical cancer, diagnostic algorithms discriminated patients from controls, patients with good/bad prognosis, and with/without response to chemotherapy. In endometrial cancer, several models stratified patients from controls and recurrent from non-recurrent patients. Metabolomics is valuable for constructing diagnostic models. However, the majority of studies were in the discovery phase and require additional research to select reliable biomarkers for validation and translation into clinical practice. This review identifies bottlenecks that currently prevent the translation of these findings into clinical practice.
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Affiliation(s)
- Janina Tokarz
- Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Centre for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany; (J.T.); (J.A.)
| | - Jerzy Adamski
- Research Unit Molecular Endocrinology and Metabolism, Helmholtz Zentrum München, German Research Centre for Environmental Health, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany; (J.T.); (J.A.)
- German Centre for Diabetes Research, Ingolstaedter Landstrasse 1, 85764 Neuherberg, Germany
- Lehrstuhl für Experimentelle Genetik, Technische Universität München, Freising-Weihenstephan, 85764 Neuherberg, Germany
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117596, Singapore
| | - Tea Lanišnik Rižner
- Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia
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Reçber T, Nemutlu E, Beksaç K, Aksoy S, Kır S. Optimization and validation of a HILIC-LC-ESI-MS/MS method for the simultaneous analysis of targeted metabolites: Cross validation of untargeted metabolomic studies for early diagnosis of breast cancer. Microchem J 2020. [DOI: 10.1016/j.microc.2020.105559] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
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27
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Ahmed-Salim Y, Galazis N, Bracewell-Milnes T, Phelps DL, Jones BP, Chan M, Munoz-Gonzales MD, Matsuzono T, Smith JR, Yazbek J, Krell J, Ghaem-Maghami S, Saso S. The application of metabolomics in ovarian cancer management: a systematic review. Int J Gynecol Cancer 2020; 31:754-774. [PMID: 33106272 DOI: 10.1136/ijgc-2020-001862] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2020] [Revised: 09/24/2020] [Accepted: 09/28/2020] [Indexed: 12/15/2022] Open
Abstract
Metabolomics, the global analysis of metabolites in a biological specimen, could potentially provide a fast method of biomarker identification for ovarian cancer. This systematic review aims to examine findings from studies that apply metabolomics to the diagnosis, prognosis, treatment, and recurrence of ovarian cancer. A systematic search of English language publications was conducted on PubMed, Science Direct, and SciFinder. It was augmented by a snowball strategy, whereby further relevant studies are identified from reference lists of included studies. Studies in humans with ovarian cancer which focus on metabolomics of biofluids and tumor tissue were included. No restriction was placed on the time of publication. A separate review of targeted metabolomic studies was conducted for completion. Qualitative data were summarized in a comprehensive table. The studies were assessed for quality and risk of bias using the ROBINS-I tool. 32 global studies were included in the main systematic review. Most studies applied metabolomics to diagnosing ovarian cancer, within which the most frequently reported metabolite changes were a down-regulation of phospholipids and amino acids: histidine, citrulline, alanine, and methionine. Dysregulated phospholipid metabolism was also reported in the separately reviewed 18 targeted studies. Generally, combinations of more than one significant metabolite as a panel, in different studies, achieved a higher sensitivity and specificity for diagnosis than a single metabolite; for example, combinations of different phospholipids. Widespread metabolite differences were observed in studies examining prognosis, treatment, and recurrence, and limited conclusions could be drawn. Cellular processes of proliferation and invasion may be reflected in metabolic changes present in poor prognosis and recurrence. For example, lower levels of lysine, with increased cell invasion as an underlying mechanism, or glutamine dependency of rapidly proliferating cancer cells. In conclusion, this review highlights potential metabolites and biochemical pathways which may aid the clinical care of ovarian cancer if further validated.
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Affiliation(s)
| | - Nicolas Galazis
- Department of Obstetrics and Gynaecology, Northwick Park Hospital, Harrow, UK
| | | | - David L Phelps
- Department of Gynaecological Oncology, Hammersmith Hospital Campus, Du Cane Road, Imperial College Healthcare NHS Trust, London, UK
| | - Benjamin P Jones
- Division of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, Du Cane Road, Imperial College London, London, UK
| | - Maxine Chan
- South Kensington Campus, Imperial College London Department of Materials, London, UK
| | | | - Tomoko Matsuzono
- Queen Elizabeth Hospital, Department of Obstetrics and Gynaecology, Hong Kong, Hong Kong
| | - James Richard Smith
- West London Gynaecological Cancer Centre, Queen Charlotte's Hospital, Hammersmith Hospital Campus, Du Cane Road, Imperial College Healthcare NHS Trust, London, UK
| | - Joseph Yazbek
- West London Gynaecological Cancer Centre, Queen Charlotte's Hospital, Hammersmith Hospital Campus, Du Cane Road, Imperial College Healthcare NHS Trust, London, UK
| | - Jonathan Krell
- West London Gynaecological Cancer Centre, Queen Charlotte's Hospital, Hammersmith Hospital Campus, Du Cane Road, Imperial College Healthcare NHS Trust, London, UK
| | - Sadaf Ghaem-Maghami
- Department of Gynaecological Oncology, West London Gynaecological Cancer Centre, Queen Charlotte's Hospital, Hammersmith Hospital Campus, Imperial College London and NHS Trust, Du Cane Road, Imperial College London, London, UK
| | - Srdjan Saso
- Division of Surgery and Cancer, Institute of Reproductive and Developmental Biology, Hammersmith Hospital Campus, Du Cane Road, Imperial College London, London, UK
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Saorin A, Di Gregorio E, Miolo G, Steffan A, Corona G. Emerging Role of Metabolomics in Ovarian Cancer Diagnosis. Metabolites 2020; 10:E419. [PMID: 33086611 PMCID: PMC7603269 DOI: 10.3390/metabo10100419] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 10/14/2020] [Accepted: 10/15/2020] [Indexed: 01/20/2023] Open
Abstract
Ovarian cancer is considered a silent killer due to the lack of clear symptoms and efficient diagnostic tools that often lead to late diagnoses. Over recent years, the impelling need for proficient biomarkers has led researchers to consider metabolomics, an emerging omics science that deals with analyses of the entire set of small-molecules (≤1.5 kDa) present in biological systems. Metabolomics profiles, as a mirror of tumor-host interactions, have been found to be useful for the analysis and identification of specific cancer phenotypes. Cancer may cause significant metabolic alterations to sustain its growth, and metabolomics may highlight this, making it possible to detect cancer in an early phase of development. In the last decade, metabolomics has been widely applied to identify different metabolic signatures to improve ovarian cancer diagnosis. The aim of this review is to update the current status of the metabolomics research for the discovery of new diagnostic metabolomic biomarkers for ovarian cancer. The most promising metabolic alterations are discussed in view of their potential biological implications, underlying the issues that limit their effective clinical translation into ovarian cancer diagnostic tools.
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Affiliation(s)
- Asia Saorin
- Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; (A.S.); (E.D.G.); (A.S.)
| | - Emanuela Di Gregorio
- Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; (A.S.); (E.D.G.); (A.S.)
| | - Gianmaria Miolo
- Medical Oncology and Cancer Prevention Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy;
| | - Agostino Steffan
- Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; (A.S.); (E.D.G.); (A.S.)
| | - Giuseppe Corona
- Immunopathology and Cancer Biomarkers Unit, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, 33081 Aviano, Italy; (A.S.); (E.D.G.); (A.S.)
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Li J, Guan X, Fan Z, Ching LM, Li Y, Wang X, Cao WM, Liu DX. Non-Invasive Biomarkers for Early Detection of Breast Cancer. Cancers (Basel) 2020; 12:E2767. [PMID: 32992445 PMCID: PMC7601650 DOI: 10.3390/cancers12102767] [Citation(s) in RCA: 107] [Impact Index Per Article: 21.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2020] [Revised: 09/23/2020] [Accepted: 09/24/2020] [Indexed: 12/24/2022] Open
Abstract
Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of "omics" strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.
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Affiliation(s)
- Jiawei Li
- The Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand; (J.L.); (X.G.); (Y.L.)
| | - Xin Guan
- The Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand; (J.L.); (X.G.); (Y.L.)
- Department of Breast Surgery, the First Hospital of Jilin University, Jilin University, Changchun 130021, China;
| | - Zhimin Fan
- Department of Breast Surgery, the First Hospital of Jilin University, Jilin University, Changchun 130021, China;
| | - Lai-Ming Ching
- Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1023, New Zealand;
| | - Yan Li
- The Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand; (J.L.); (X.G.); (Y.L.)
| | - Xiaojia Wang
- Department of Breast Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital & Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Wen-Ming Cao
- Department of Breast Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital & Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China;
| | - Dong-Xu Liu
- The Centre for Biomedical and Chemical Sciences, School of Science, Faculty of Health and Environmental Sciences, Auckland University of Technology, Auckland 1010, New Zealand; (J.L.); (X.G.); (Y.L.)
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30
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Laser-assisted rapid evaporative ionisation mass spectrometry (LA-REIMS) as a metabolomics platform in cervical cancer screening. EBioMedicine 2020; 60:103017. [PMID: 32980699 PMCID: PMC7522750 DOI: 10.1016/j.ebiom.2020.103017] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 08/31/2020] [Accepted: 09/08/2020] [Indexed: 12/12/2022] Open
Abstract
Background The introduction of high-risk human papillomavirus (hrHPV) testing as part of primary cervical screening is anticipated to improve sensitivity, but also the number of women who will screen positive. Reflex cytology is the preferred triage test in most settings but has limitations including moderate diagnostic accuracy, lack of automation, inter-observer variability and the need for clinician-collected sample. Novel, objective and cost-effective approaches are needed. Methods In this study, we assessed the potential use of an automated metabolomic robotic platform, employing the principle of laser-assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) in cervical cancer screening. Findings In a population of 130 women, LA-REIMS achieved 94% sensitivity and 83% specificity (AUC: 91.6%) in distinguishing women testing positive (n = 65) or negative (n = 65) for hrHPV. We performed further analysis according to disease severity with LA-REIMS achieving sensitivity and specificity of 91% and 73% respectively (AUC: 86.7%) in discriminating normal from high-grade pre-invasive disease. Interpretation This automated high-throughput technology holds promise as a low-cost and rapid test for cervical cancer screening and triage. The use of platforms like LA-REIMS has the potential to further improve the accuracy and efficiency of the current national screening programme. Funding Work was funded by the MRC Imperial Confidence in Concept Scheme, Imperial College Healthcare Charity, British Society for Colposcopy and Cervical Pathology, National Research Development and Innovation Office of Hungary, Waters corporation and NIHR BRC.
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31
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Rashed R, Darwish H, Omran M, Belal A, Zahran F. A novel serum metabolome score for breast cancer diagnosis. Br J Biomed Sci 2020; 77:196-201. [DOI: 10.1080/09674845.2020.1784568] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Affiliation(s)
- R Rashed
- Chemistry Department, Faculty of Science, Port Said University, Port Said, Egypt
| | - H Darwish
- Damietta Cancer Institute, Damietta/Ismailia Teaching Oncology Hospital, Ismailia, Egypt
| | - M Omran
- Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt
| | - A Belal
- Chemistry Department, Faculty of Science, Port Said University, Port Said, Egypt
| | - F Zahran
- Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt
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32
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Yang L, Wang Y, Cai H, Wang S, Shen Y, Ke C. Application of metabolomics in the diagnosis of breast cancer: a systematic review. J Cancer 2020; 11:2540-2551. [PMID: 32201524 PMCID: PMC7066003 DOI: 10.7150/jca.37604] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2019] [Accepted: 12/31/2019] [Indexed: 12/24/2022] Open
Abstract
Breast cancer (BC) remains the most frequent type of cancer in females worldwide. However, the pathogenesis of BC is still under the cloud, along with the huge challenge of early diagnosis, which is widely acknowledged as the key to a successful therapy. Metabolomics, a newborn innovative technique in recent years, has demonstrated great potential in cancer-related researches. The aim of this review is to look back on clinical and cellular metabolomic studies in the diagnosis of BC over the past decade, and provide a systematic summary of metabolic biomarkers and pathways related to BC diagnosis.
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Affiliation(s)
- Liqing Yang
- Medical College of Soochow University, Suzhou 215123, P. R. China
| | - Ying Wang
- Medical College of Soochow University, Suzhou 215123, P. R. China
| | - Haishan Cai
- Medical College of Soochow University, Suzhou 215123, P. R. China
| | - Shuang Wang
- Medical College of Soochow University, Suzhou 215123, P. R. China
| | - Yueping Shen
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, P. R. China
| | - Chaofu Ke
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College of Soochow University, 199 Renai Road, Suzhou 215123, P. R. China
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33
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Dinges SS, Hohm A, Vandergrift LA, Nowak J, Habbel P, Kaltashov IA, Cheng LL. Cancer metabolomic markers in urine: evidence, techniques and recommendations. Nat Rev Urol 2020; 16:339-362. [PMID: 31092915 DOI: 10.1038/s41585-019-0185-3] [Citation(s) in RCA: 102] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Urinary tests have been used as noninvasive, cost-effective tools for screening, diagnosis and monitoring of diseases since ancient times. As we progress through the 21st century, modern analytical platforms have enabled effective measurement of metabolites, with promising results for both a deeper understanding of cancer pathophysiology and, ultimately, clinical translation. The first study to measure metabolomic urinary cancer biomarkers using NMR and mass spectrometry (MS) was published in 2006 and, since then, these techniques have been used to detect cancers of the urological system (kidney, prostate and bladder) and nonurological tumours including those of the breast, ovary, lung, liver, gastrointestinal tract, pancreas, bone and blood. This growing field warrants an assessment of the current status of research developments and recommendations to help systematize future research.
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Affiliation(s)
- Sarah S Dinges
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Haematology and Oncology, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Annika Hohm
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Diagnostic and Interventional Neuroradiology, University Hospital of Würzburg, Würzburg, Germany
| | - Lindsey A Vandergrift
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Johannes Nowak
- Department of Diagnostic and Interventional Radiology, University Hospital of Würzburg, Würzburg, Germany
| | - Piet Habbel
- Department of Haematology and Oncology, CCM, Charité-Universitätsmedizin Berlin, Berlin, Germany
| | - Igor A Kaltashov
- Department of Chemistry, University of Massachusetts-Amherst, Amherst, MA, USA.
| | - Leo L Cheng
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. .,Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
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Graça G, Lau CHE, Gonçalves LG. Exploring Cancer Metabolism: Applications of Metabolomics and Metabolic Phenotyping in Cancer Research and Diagnostics. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1219:367-385. [PMID: 32130709 DOI: 10.1007/978-3-030-34025-4_19] [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] [Indexed: 12/26/2022]
Abstract
Altered metabolism is one of the key hallmarks of cancer. The development of sensitive, reproducible and robust bioanalytical tools such as Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry techniques offers numerous opportunities for cancer metabolism research, and provides additional and exciting avenues in cancer diagnosis, prognosis and for the development of more effective and personalized treatments. In this chapter, we introduce the current state of the art of metabolomics and metabolic phenotyping approaches in cancer research and clinical diagnostics.
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Affiliation(s)
- Gonçalo Graça
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK.
| | - Chung-Ho E Lau
- Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, UK
| | - Luís G Gonçalves
- Proteomics of Non-Model Organisms Lab, ITQB Nova-Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.
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Silva CL, Olival A, Perestrelo R, Silva P, Tomás H, Câmara JS. Untargeted Urinary 1H NMR-Based Metabolomic Pattern as a Potential Platform in Breast Cancer Detection. Metabolites 2019; 9:E269. [PMID: 31703396 PMCID: PMC6918409 DOI: 10.3390/metabo9110269] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Revised: 10/25/2019] [Accepted: 11/06/2019] [Indexed: 12/24/2022] Open
Abstract
Breast cancer (BC) remains the second leading cause of death among women worldwide. An emerging approach based on the identification of endogenous metabolites (EMs) and the establishment of the metabolomic fingerprint of biological fluids constitutes a new frontier in medical diagnostics and a promising strategy to differentiate cancer patients from healthy individuals. In this work we aimed to establish the urinary metabolomic patterns from 40 BC patients and 38 healthy controls (CTL) using proton nuclear magnetic resonance spectroscopy (1H-NMR) as a powerful approach to identify a set of BC-specific metabolites which might be employed in the diagnosis of BC. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was applied to a 1H-NMR processed data matrix. Metabolomic patterns distinguished BC from CTL urine samples, suggesting a unique metabolite profile for each investigated group. A total of 10 metabolites exhibited the highest contribution towards discriminating BC patients from healthy controls (variable importance in projection (VIP) >1, p < 0.05). The discrimination efficiency and accuracy of the urinary EMs were ascertained by receiver operating characteristic curve (ROC) analysis that allowed the identification of some metabolites with the highest sensitivities and specificities to discriminate BC patients from healthy controls (e.g. creatine, glycine, trimethylamine N-oxide, and serine). The metabolomic pathway analysis indicated several metabolism pathway disruptions, including amino acid and carbohydrate metabolisms, in BC patients, namely, glycine and butanoate metabolisms. The obtained results support the high throughput potential of NMR-based urinary metabolomics patterns in discriminating BC patients from CTL. Further investigations could unravel novel mechanistic insights into disease pathophysiology, monitor disease recurrence, and predict patient response towards therapy.
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Affiliation(s)
- Catarina L. Silva
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal; (C.L.S.); (A.O.); (R.P.); (P.S.); (H.T.)
| | - Ana Olival
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal; (C.L.S.); (A.O.); (R.P.); (P.S.); (H.T.)
| | - Rosa Perestrelo
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal; (C.L.S.); (A.O.); (R.P.); (P.S.); (H.T.)
| | - Pedro Silva
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal; (C.L.S.); (A.O.); (R.P.); (P.S.); (H.T.)
| | - Helena Tomás
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal; (C.L.S.); (A.O.); (R.P.); (P.S.); (H.T.)
- Faculdade de Ciências Exactas e Engenharia da Universidade da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal
| | - José S. Câmara
- CQM—Centro de Química da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal; (C.L.S.); (A.O.); (R.P.); (P.S.); (H.T.)
- Faculdade de Ciências Exactas e Engenharia da Universidade da Madeira, Universidade da Madeira, Campus Universitário da Penteada, 9020-105 Funchal, Portugal
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MacMullan MA, Dunn ZS, Graham NA, Yang L, Wang P. Quantitative Proteomics and Metabolomics Reveal Biomarkers of Disease as Potential Immunotherapy Targets and Indicators of Therapeutic Efficacy. Theranostics 2019; 9:7872-7888. [PMID: 31695805 PMCID: PMC6831481 DOI: 10.7150/thno.37373] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 08/19/2019] [Indexed: 02/07/2023] Open
Abstract
Quantitative mass spectrometry (MS) continues to deepen our understanding of the immune system, quickly becoming the gold standard for obtaining high-throughput, quantitative data on biomolecules. The development of targeted and multiplexed assays for biomarker quantification makes MS an attractive tool both for diagnosing diseases and for quantifying the effects of immunotherapeutics. Because of its accuracy, the use of MS for identifying biomarkers of disease reduces the potential for misdiagnosis and overtreatment. Advances in workflows for sample processing have drastically reduced processing time and complexities due to sample preparation, making MS a more accessible technology. In this review, we present how recent developments in proteomics and metabolomics make MS an essential component of enhancing and monitoring the efficacy of immunotherapeutic treatments.
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Affiliation(s)
- Melanie A. MacMullan
- Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California
| | - Zachary S. Dunn
- Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California
| | - Nicholas A. Graham
- Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California
| | - Lili Yang
- Department of Microbiology, Immunology & Molecular Genetics, University of California, Los Angeles, California
- Eli & Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, California
| | - Pin Wang
- Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, California
- Department of Biomedical Engineering, University of Southern California, Los Angeles, California
- Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, California
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Review and Comparison of Cancer Biomarker Trends in Urine as a Basis for New Diagnostic Pathways. Cancers (Basel) 2019; 11:cancers11091244. [PMID: 31450698 PMCID: PMC6770126 DOI: 10.3390/cancers11091244] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 08/20/2019] [Accepted: 08/22/2019] [Indexed: 12/24/2022] Open
Abstract
Cancer is one of the major causes of mortality worldwide and its already large burden is projected to increase significantly in the near future with a predicted 22 million new cancer cases and 13 million cancer-related deaths occurring annually by 2030. Unfortunately, current procedures for diagnosis are characterized by low diagnostic accuracies. Given the proved correlation between cancer presence and alterations of biological fluid composition, many researchers suggested their characterization to improve cancer detection at early stages. This paper reviews the information that can be found in the scientific literature, regarding the correlation of different cancer forms with the presence of specific metabolites in human urine, in a schematic and easily interpretable form, because of the huge amount of relevant literature. The originality of this paper relies on the attempt to point out the odor properties of such metabolites, and thus to highlight the correlation between urine odor alterations and cancer presence, which is proven by recent literature suggesting the analysis of urine odor for diagnostic purposes. This investigation aims to evaluate the possibility to compare the results of studies based on different approaches to be able in the future to identify those compounds responsible for urine odor alteration.
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Huang D, Gaul DA, Nan H, Kim J, Fernández FM. Deep Metabolomics of a High-Grade Serous Ovarian Cancer Triple-Knockout Mouse Model. J Proteome Res 2019; 18:3184-3194. [PMID: 31290664 DOI: 10.1021/acs.jproteome.9b00263] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
High-grade serous carcinoma (HGSC) is the most common and deadliest ovarian cancer (OC) type, accounting for 70-80% of OC deaths. This high mortality is largely due to late diagnosis. Early detection is thus crucial to reduce mortality, yet the tumor pathogenesis of HGSC remains poorly understood, making early detection exceedingly difficult. Faithfully and reliably representing the clinical nature of human HGSC, a recently developed triple-knockout (TKO) mouse model offers a unique opportunity to examine the entire disease spectrum of HGSC. Metabolic alterations were investigated by applying ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to serum samples collected from these mice at premalignant, early, and advanced stages of HGSC. This comprehensive analysis revealed a panel of 29 serum metabolites that distinguished mice with HGSC from controls and mice with uterine tumors with over 95% accuracy. Meanwhile, our panel could further distinguish early-stage HGSC from controls with 100% accuracy and from advanced-stage HGSC with over 90% accuracy. Important identified metabolites included phospholipids, sphingomyelins, sterols, N-acyltaurine, oligopeptides, bilirubin, 2(3)-hydroxysebacic acids, uridine, N-acetylneuraminic acid, and pyrazine derivatives. Overall, our study provides insights into dysregulated metabolism associated with HGSC development and progression, and serves as a useful guide toward early detection.
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Affiliation(s)
- Danning Huang
- School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States
| | - David A Gaul
- School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States
| | | | | | - Facundo M Fernández
- School of Chemistry and Biochemistry , Georgia Institute of Technology , Atlanta , Georgia 30332 , United States
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Jain A, Li XH, Chen WN. An untargeted fecal and urine metabolomics analysis of the interplay between the gut microbiome, diet and human metabolism in Indian and Chinese adults. Sci Rep 2019; 9:9191. [PMID: 31235863 PMCID: PMC6591403 DOI: 10.1038/s41598-019-45640-y] [Citation(s) in RCA: 61] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2018] [Accepted: 06/07/2019] [Indexed: 01/08/2023] Open
Abstract
Gut microbiome plays a vital role in human health. Human fecal and urine metabolome could provide a functional readout of gut microbial metabolism as well as its interaction with host and diet. However, this relationship still needs to be fully characterized. We established an untargeted GC-MS metabolomics method which enabled the detection of 122 and 86 metabolites including amino acids, phenolics, indoles, carbohydrates, sugars and metabolites of microbial origin from fecal and urine samples respectively. 41 compounds were confirmed using external standards. Next, we compared the fecal and urine metabolome of 16 healthy Indian and Chinese adults, ages 22–35 years, using a combined GC-MS and LC-MS approach. We showed dietary habit or ethnicity wise grouping of urine and fecal metabolite profiles of Indian and Chinese adults. Our analysis revealed 53 differentiating metabolites including higher abundance of amino acids and phenolics in Chinese and higher abundance of fatty acids, glycocholic acid, metabolites related to tryptophan metabolism in Indian adults. Correlation analysis showed a strong association of metabolites with gut bacterial profiles of the same subjects in the genus and species level. Thus, our results suggest that gut bacterial compositional changes could be eventually monitored and probed using a metabolomics approach.
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Affiliation(s)
- Abhishek Jain
- Interdisciplinary Graduate School, Nanyang Technological University, 50 Nanyang Avenue, Singapore, 639798, Singapore.,Advanced Environmental Biotechnology Centre, Nanyang Environment & Water Research Institute, Nanyang Technological University, 1 CleanTech Loop, Singapore, 637141, Singapore
| | - Xin Hui Li
- Zhong Feng International, Hengyang City, China
| | - Wei Ning Chen
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, Singapore, 637459, Singapore.
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NMR-Based Metabolomics in Metal-Based Drug Research. Molecules 2019; 24:molecules24122240. [PMID: 31208065 PMCID: PMC6630333 DOI: 10.3390/molecules24122240] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 06/12/2019] [Accepted: 06/13/2019] [Indexed: 12/24/2022] Open
Abstract
Thanks to recent advances in analytical technologies and statistical capabilities, the application field of metabolomics has increased significantly. Currently, this approach is used to investigate biological substrates looking for metabolic profile alterations, diseases markers, and drug effects. In particular, NMR spectroscopy has shown great potential as a detection technique, mainly for the ability to detect multiple (10s to 100s) metabolites at once without separation. Only in recent years has the NMR-based metabolomic approach been extended to investigate the cell metabolic alterations induced by metal-based antitumor drug administration. As expected, these studies are mainly focused on platinum complexes, but some palladium and ruthenium compounds are also under investigation. The use of a metabolomics approach was very effective in assessing tumor response to drugs and providing insights into the mechanism of action and resistance. Therefore, metabolomics may open new perspectives into the development of metal-based drugs. In particular, it has been shown that NMR-based, in vitro metabolomics is a powerful tool for detecting variations of the cell metabolites induced by the metal drug exposure, thus offering also the possibility of identifying specific markers for in vivo monitoring of tumor responsiveness to anticancer treatments.
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Hair Metabolomics in Animal Studies and Clinical Settings. Molecules 2019; 24:molecules24122195. [PMID: 31212725 PMCID: PMC6630908 DOI: 10.3390/molecules24122195] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2019] [Revised: 06/11/2019] [Accepted: 06/11/2019] [Indexed: 12/12/2022] Open
Abstract
Metabolomics is a powerful tool used to understand comprehensive changes in the metabolic response and to study the phenotype of an organism by instrumental analysis. It most commonly involves mass spectrometry followed by data mining and metabolite assignment. For the last few decades, hair has been used as a valuable analytical sample to investigate retrospective xenobiotic exposure as it provides a wider window of detection than other biological samples such as saliva, plasma, and urine. Hair contains functional metabolomes such as amino acids and lipids. Moreover, segmental analysis of hair based on its growth rate can provide information on metabolic changes over time. Therefore, it has great potential as a metabolomics sample to monitor chronic diseases, including drug addiction or abnormal conditions. In the current review, the latest applications of hair metabolomics in animal studies and clinical settings are highlighted. For this purpose, we review and discuss the characteristics of hair as a metabolomics sample, the analytical techniques employed in hair metabolomics and the consequence of hair metabolome alterations in recent studies. Through this, the value of hair as an alternative biological sample in metabolomics is highlighted.
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Burton C, Ma Y. Current Trends in Cancer Biomarker Discovery Using Urinary Metabolomics: Achievements and New Challenges. Curr Med Chem 2019; 26:5-28. [PMID: 28914192 DOI: 10.2174/0929867324666170914102236] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Revised: 07/26/2016] [Accepted: 08/08/2016] [Indexed: 12/20/2022]
Abstract
BACKGROUND The development of effective screening methods for early cancer detection is one of the foremost challenges facing modern cancer research. Urinary metabolomics has recently emerged as a potentially transformative approach to cancer biomarker discovery owing to its noninvasive sampling characteristics and robust analytical feasibility. OBJECTIVE To provide an overview of new developments in urinary metabolomics, cover the most promising aspects of hyphenated techniques in untargeted and targeted metabolomics, and to discuss technical and clinical limitations in addition to the emerging challenges in the field of urinary metabolomics and its application to cancer biomarker discovery. METHODS A systematic review of research conducted in the past five years on the application of urinary metabolomics to cancer biomarker discovery was performed. Given the breadth of this topic, our review focused on the five most widely studied cancers employing urinary metabolomics approaches, including lung, breast, bladder, prostate, and ovarian cancers. RESULTS As an extension of conventional metabolomics, urinary metabolomics has benefitted from recent technological developments in nuclear magnetic resonance, mass spectrometry, gas and liquid chromatography, and capillary electrophoresis that have improved urine metabolome coverage and analytical reproducibility. Extensive metabolic profiling in urine has revealed a significant number of altered metabolic pathways and putative biomarkers, including pteridines, modified nucleosides, and acylcarnitines, that have been associated with cancer development and progression. CONCLUSION Urinary metabolomics presents a transformative new approach toward cancer biomarker discovery with high translational capacity to early cancer screening.
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Affiliation(s)
- Casey Burton
- Department of Chemistry and Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO, United States
| | - Yinfa Ma
- Department of Chemistry and Center for Single Nanoparticle, Single Cell, and Single Molecule Monitoring, Missouri University of Science and Technology, Rolla, MO, United States
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Lu X, Li Y, Xia B, Bai Y, Zhang K, Zhang X, Xie H, Sun F, Hou Y, Li K. Selection of small plasma peptides for the auxiliary diagnosis and prognosis of epithelial ovarian cancer by using UPLC/MS‐based nontargeted and targeted analyses. Int J Cancer 2019; 144:2033-2042. [DOI: 10.1002/ijc.31807] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2018] [Revised: 07/14/2018] [Accepted: 07/31/2018] [Indexed: 12/30/2022]
Affiliation(s)
- Xin Lu
- School of Life Science and TechnologyHarbin Institute of Technology Harbin China
| | - Yiqun Li
- School of Life Science and TechnologyHarbin Institute of Technology Harbin China
| | - Bairong Xia
- Department of GynecologyThe Affiliated Tumor Hospital of Harbin Medical University Harbin China
| | - Yunfan Bai
- School of Life Science and TechnologyHarbin Institute of Technology Harbin China
| | - Kun Zhang
- School of Life Science and TechnologyHarbin Institute of Technology Harbin China
| | - Xiaohan Zhang
- School of Life Science and TechnologyHarbin Institute of Technology Harbin China
| | - Hongyu Xie
- Department of Epidemiology and BiostatisticsSchool of Public Health, Harbin Medical University Harbin China
| | - Fengyu Sun
- Department of CardiologyThe First Affiliated Hospital of Harbin Medical University Harbin China
| | - Yan Hou
- Department of Epidemiology and BiostatisticsSchool of Public Health, Harbin Medical University Harbin China
| | - Kang Li
- Department of Epidemiology and BiostatisticsSchool of Public Health, Harbin Medical University Harbin China
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Garg G, Yilmaz A, Kumar P, Turkoglu O, Mutch DG, Powell MA, Rosen B, Bahado-Singh RO, Graham SF. Targeted metabolomic profiling of low and high grade serous epithelial ovarian cancer tissues: a pilot study. Metabolomics 2018; 14:154. [PMID: 30830441 DOI: 10.1007/s11306-018-1448-3] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2018] [Accepted: 10/31/2018] [Indexed: 01/12/2023]
Abstract
INTRODUCTION Epithelial ovarian cancer (EOC) remains the leading cause of death from gynecologic malignancies and has an alarming global fatality rate. Besides the differences in underlying pathogenesis, distinguishing between high grade (HG) and low grade (LG) EOC is imperative for the prediction of disease progression and responsiveness to chemotherapy. OBJECTIVES The aim of this study was to investigate, the tissue metabolome associated with HG and LG serous epithelial ovarian cancer. METHODS A combination of one dimensional proton nuclear magnetic resonance (1D H NMR) spectroscopy and targeted mass spectrometry (MS) was employed to profile the tissue metabolome of HG, LG serous EOCs, and controls. RESULTS Using partial least squares-discriminant analysis, we observed significant separation between all groups (p < 0.05) following cross validation. We identified which metabolites were significantly perturbed in each EOC grade as compared with controls and report the biochemical pathways which were perturbed due to the disease. Among these metabolic pathways, ascorbate and aldarate metabolism was identified, for the first time, as being significantly altered in both LG and HG serous cancers. Further, we have identified potential biomarkers of EOC and generated predictive algorithms with AUC (CI) = 0.940 and 0.929 for HG and LG, respectively. CONCLUSION These previously unreported biochemical changes provide a framework for future metabolomic studies for the development of EOC biomarkers. Finally, pharmacologic targeting of the key metabolic pathways identified herein could lead to novel and effective treatments of EOC.
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Affiliation(s)
- Gunjal Garg
- Karmanos Cancer Institute Mclaren Flint, 4100 Beecher Road, 48532, Flint, MI, USA
| | - Ali Yilmaz
- Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, USA.
| | - Praveen Kumar
- Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, USA
| | - Onur Turkoglu
- Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, USA
| | - David G Mutch
- Department of Obstetrics and Gynecology, Washington University School of Medicine, 660 S. Euclid Ave. CB 8064, St. Louis, MO, USA
| | - Matthew A Powell
- Department of Obstetrics and Gynecology, Washington University School of Medicine, 660 S. Euclid Ave. CB 8064, St. Louis, MO, USA
| | - Barry Rosen
- Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, USA
| | - Ray O Bahado-Singh
- Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, USA
| | - Stewart F Graham
- Department of Obstetrics and Gynecology, William Beaumont Health, Royal Oak, MI, USA
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Metabolomic profiling suggests long chain ceramides and sphingomyelins as a possible diagnostic biomarker of epithelial ovarian cancer. Clin Chim Acta 2018; 481:108-114. [DOI: 10.1016/j.cca.2018.02.029] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Revised: 02/22/2018] [Accepted: 02/22/2018] [Indexed: 12/30/2022]
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Oh J, Yoon DH, Han JG, Choi HK, Sung GH. 1H NMR based metabolite profiling for optimizing the ethanol extraction of Wolfiporia cocos. Saudi J Biol Sci 2018; 25:1128-1134. [PMID: 30174512 PMCID: PMC6117373 DOI: 10.1016/j.sjbs.2018.04.007] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Revised: 04/02/2018] [Accepted: 04/04/2018] [Indexed: 02/06/2023] Open
Abstract
Metabolite profiling of Wolfiporia cocos (family: Polyporaceae) had been much advancement in recent days, and its analysis by nuclear magnetic resonance (NMR) spectroscopy has become well established. However, the highly important trait of W. cocos still needs advanced protocols despite some standardization. Partial least squares discriminant analysis (PLS-DA) was used as the multivariate statistical analysis of the 1H NMR data set. The PLS-DA model was validated, and the key metabolites contributing to the separation in the score plots of different ethanol W. cocos extract. 1H NMR spectroscopy of W. cocos identified 33 chemically diverse metabolites in D2O, consisting of 13 amino acids, 11 organic acids 2 sugars, 3 sugar alcohols, 1 nucleoside, and 3 others. Among these metabolites, the levels of tyrosine, proline, methionine, sarcosine, choline, acetoacetate, citrate, 4-aminobutyrate, aspartate, maltose, malate, lysine, xylitol, lactate threonine, leucine, valine, isoleucine, uridine, guanidoacetate, arabitol, mannitol, glucose, and betaine were increased in the 95% ethanol extraction sample compared with the levels in other samples, whereas level of acetate, phenylalanine, alanine, succinate, and fumarate were significantly increased in the 0% ethanol extraction sample. A biological triterpenoid, namely pachymic acid, was detected from different ethanol P. cocos extract using 1H-NMR spectra were found in CDCl3. This is the first report to perform the metabolomics profiling of different ethanol W. cocos extract. These researches suggest that W. cocos can be used to obtain substantial amounts of bioactive ingredients for use as potential pharmacological and nutraceuticals agents.
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Affiliation(s)
- Junsang Oh
- Institute for Healthcare and Life Science, International St. Mary’s Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea
- College of Pharmacy, Chung-Ang University, Republic of Korea
| | - Deok-Hyo Yoon
- Institute for Healthcare and Life Science, International St. Mary’s Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea
| | - Jae-Gu Han
- Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Republic of Korea
| | - Hyung-Kyoon Choi
- College of Pharmacy, Chung-Ang University, Republic of Korea
- Corresponding authors at: Institute for Healthcare and Life Science, International St. Mary’s Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea (G.-H. Sung); College of Pharmacy, Chung-Ang University, Republic of Korea (H.-K. Choi)
| | - Gi-Ho Sung
- Institute for Healthcare and Life Science, International St. Mary’s Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea
- Department of Microbiology, College of Medicine, Catholic Kwandong University, Republic of Korea
- Corresponding authors at: Institute for Healthcare and Life Science, International St. Mary’s Hospital and College of Medicine, Catholic Kwandong University, Incheon 22711, Republic of Korea (G.-H. Sung); College of Pharmacy, Chung-Ang University, Republic of Korea (H.-K. Choi)
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Patejko M, Struck-Lewicka W, Siluk D, Waszczuk-Jankowska M, Markuszewski MJ. Urinary Nucleosides and Deoxynucleosides. Adv Clin Chem 2018; 83:1-51. [PMID: 29304899 DOI: 10.1016/bs.acc.2017.10.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Urinary nucleosides and deoxynucleosides are mainly known as metabolites of RNA turnover and oxidative damage of DNA. For several decades these metabolites have been examined for their potential use in disease states including cancer and oxidative stress. Subsequent improvements in analytical sensitivity and specificity have provided a reliable means to measure these unique molecules to better assess their relationship to physiologic and pathophysiologic conditions. In fact, some are currently used as antiviral and antitumor agents. In this review we provide insight into their molecular characteristics, highlight current separation techniques and detection methods, and explore potential clinical usefulness.
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Khamis MM, Adamko DJ, El-Aneed A. Development of a validated LC- MS/MS method for the quantification of 19 endogenous asthma/COPD potential urinary biomarkers. Anal Chim Acta 2017; 989:45-58. [PMID: 28915942 DOI: 10.1016/j.aca.2017.08.007] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2017] [Revised: 06/19/2017] [Accepted: 08/03/2017] [Indexed: 11/27/2022]
Abstract
Obstructive airways inflammatory diseases sometimes show overlapping symptoms that hinder their early and correct diagnosis. Current clinical tests are tedious and are of inadequate specificity in special population such as the elderly and children. Therefore, we are developing tandem mass spectrometric (MS/MS) methods for targeted analysis of urine biomarkers. Recently, proton-nuclear magnetic resonance (1H-NMR) analysis proposed 50 urinary metabolites as potential diagnostic biomarkers among asthma and chronic obstructive pulmonary disease (COPD) patients. Metabolites are divided into 3 groups based on chemical nature. For group 1 (amines and phenols, 19 urinary metabolites), we developed and validated a high performance liquid chromatographic (HPLC)-MS/MS method using differential isotope labeling (DIL) with dansyl chloride. Method development included the optimization of the derivatization reaction, the MS/MS conditions, and the chromatographic separation. Linearity varied from 2 to 4800 ng/mL and the use of 13C2-labeled derivatives allowed for the correction of matrix effects as well as the unambiguous confirmation of the identity of each metabolite in the presence of interfering isomers in urine. Despite the challenges associated with method validation, the method was fully validated as per the food and drug administration (FDA) and the European medicines agency (EMA) recommendations. Validation criteria included linearity, precision, accuracy, dilution integrity, selectivity, carryover, and stability. Challenges in selectivity experiments included the isotopic contributions of the analyte towards its internal standard (IS), that was addressed via the optimization of the IS concentration. In addition, incurred sample analysis was performed to ensure that results from patient samples are accurate and reliable. The method was robust and reproducible and is currently being applied in a cohort of asthma and COPD patient urine samples for biomarker discovery purposes.
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Affiliation(s)
- Mona M Khamis
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada
| | - Darryl J Adamko
- Department of Pediatrics, College of Medicine, University of Saskatchewan, Saskatoon, SK, Canada
| | - Anas El-Aneed
- College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.
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Shandiz FH, Ghaffarzadegan K, Fariman SJ, Akbarzadeh M, Elyasi S, Mohammadpour AH. Evaluation of serum levels of 8-oxo-2′-deoxyguanosine as a prognostic factor in nonmetastatic breast cancer patients. BREAST CANCER MANAGEMENT 2017. [DOI: 10.2217/bmt-2017-0009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Aim: 8-OxodG protein has been introduced recently as a new biomarker for breast cancer, according to its role in tumor progression and invasion. In this study, we investigated prognostic value of 8-Oxo-2′-deoxyguanosine (8-OxodG) protein in nonmetastatic breast cancer patients excluding confounding factor. Materials & methods: Before any adjuvant chemotherapy or surgery, serum level of 8-OxodG protein was determined in 79 patients with nonmetastatic breast cancer. All patients follow up for 5 years regarding cancer recurrence and survival. Results: Cumulative risk of recurrence 5 years after the beginning of the study was 0.86 and there was no significant correlation between 8-OxodG and the recurrence rate (p = 0.78). Conclusion: The serum levels of 8-OxodG protein may not be an appropriate prognostic factor in breast cancer.
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Affiliation(s)
- Fatemeh Homaei Shandiz
- Solid Tumor Treatment Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Saeed Jahani Fariman
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mahdi Akbarzadeh
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sepideh Elyasi
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amir Hooshang Mohammadpour
- Department of Clinical Pharmacy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
- Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
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Li T, Deng P. Nuclear Magnetic Resonance technique in tumor metabolism. Genes Dis 2017; 4:28-36. [PMID: 30258906 PMCID: PMC6136591 DOI: 10.1016/j.gendis.2016.12.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2016] [Accepted: 12/05/2016] [Indexed: 12/11/2022] Open
Abstract
Cancer is one of the most serious diseases that cause an enormous number of deaths all over the world. Tumor metabolism has great discrimination from that of normal tissues. Exploring the tumor metabolism may be one of the best ways to find biomarkers for cancer detection, diagnosis and to provide novel insights into internal physiological state where subtle changes may happen in metabolite concentrations. Nuclear Magnetic Resonance (NMR) technique nowadays is a popular tool to analyze cell extracts, tissues and biological fluids, etc, since it is a relatively fast and an accurate technique to supply abundant biochemical information at molecular levels for tumor research. In this review, approaches in tumor metabolism are discussed, including sample collection, data profiling and multivariate data analysis methods etc. Some typical applications of NMR are also summarized in tumor metabolism.
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Affiliation(s)
- Ting Li
- College of Chemistry, Sichuan University, Chengdu, China
| | - Pengchi Deng
- Analytical & Testing Center, Sichuan University, Chengdu, China
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