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1
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Zhong Z, Sun MM, He M, Huang HP, Hu GY, Ma SQ, Zheng HZ, Li MY, Yao L, Cong DY, Wang HF. Proteomics and its application in the research of acupuncture: An updated review. Heliyon 2024; 10:e33233. [PMID: 39022010 PMCID: PMC11253069 DOI: 10.1016/j.heliyon.2024.e33233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 12/06/2023] [Accepted: 06/17/2024] [Indexed: 07/20/2024] Open
Abstract
As a complementary and alternative therapy, acupuncture is widely used in the prevention and treatment of various diseases. However, the understanding of the mechanism of acupuncture effects is still limited due to the lack of systematic biological validation. Notably, proteomics technologies in the field of acupuncture are rapidly evolving, and these advances are greatly contributing to the research of acupuncture. In this study, we review the progress of proteomics research in analyzing the molecular mechanisms of acupuncture for neurological disorders, pain, circulatory disorders, digestive disorders, and other diseases, with an in-depth discussion around acupoint prescription and acupuncture manipulation modalities. The study found that proteomics has great potential in understanding the mechanisms of acupuncture. This study will help explore the mechanisms of acupuncture from a proteomic perspective and provide information to support future clinical decisions.
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Affiliation(s)
- Zhen Zhong
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - Meng-Meng Sun
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - Min He
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - Hai-Peng Huang
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - Guan-Yu Hu
- The Third Affiliated Hospital of Southern Medical University, No.183, West of Zhongshan Avenue, Tianhe District, Guangzhou, 510630, Guangdong Province, China
| | - Shi-Qi Ma
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - Hai-Zhu Zheng
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - Meng-Yuan Li
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - Lin Yao
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
| | - De-Yu Cong
- Department of Tuina, Traditional Chinese Medicine Hospital of Jilin Province, 130000, Changchun, China
| | - Hong-Feng Wang
- Changchun University of Chinese Medicine, No.1035 Boshuo Road, Jingyue National High Tech Industrial Development Zone, 130117, Changchun, China
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2
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Jiang W, Jones JC, Shankavaram U, Sproull M, Camphausen K, Krauze AV. Analytical Considerations of Large-Scale Aptamer-Based Datasets for Translational Applications. Cancers (Basel) 2022; 14:2227. [PMID: 35565358 PMCID: PMC9105298 DOI: 10.3390/cancers14092227] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/15/2022] [Accepted: 04/18/2022] [Indexed: 11/17/2022] Open
Abstract
The development and advancement of aptamer technology has opened a new realm of possibilities for unlocking the biocomplexity available within proteomics. With ultra-high-throughput and multiplexing, alongside remarkable specificity and sensitivity, aptamers could represent a powerful tool in disease-specific research, such as supporting the discovery and validation of clinically relevant biomarkers. One of the fundamental challenges underlying past and current proteomic technology has been the difficulty of translating proteomic datasets into standards of practice. Aptamers provide the capacity to generate single panels that span over 7000 different proteins from a singular sample. However, as a recent technology, they also present unique challenges, as the field of translational aptamer-based proteomics still lacks a standardizing methodology for analyzing these large datasets and the novel considerations that must be made in response to the differentiation amongst current proteomic platforms and aptamers. We address these analytical considerations with respect to surveying initial data, deploying proper statistical methodologies to identify differential protein expressions, and applying datasets to discover multimarker and pathway-level findings. Additionally, we present aptamer datasets within the multi-omics landscape by exploring the intersectionality of aptamer-based proteomics amongst genomics, transcriptomics, and metabolomics, alongside pre-existing proteomic platforms. Understanding the broader applications of aptamer datasets will substantially enhance current efforts to generate translatable findings for the clinic.
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Affiliation(s)
- Will Jiang
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, CRC, Bethesda, MD 20892, USA; (W.J.); (U.S.); (M.S.); (K.C.)
| | - Jennifer C. Jones
- Translational Nanobiology Section, Laboratory of Pathology, NIH/NCI/CCR, Bethesda, MD 20892, USA;
| | - Uma Shankavaram
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, CRC, Bethesda, MD 20892, USA; (W.J.); (U.S.); (M.S.); (K.C.)
| | - Mary Sproull
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, CRC, Bethesda, MD 20892, USA; (W.J.); (U.S.); (M.S.); (K.C.)
| | - Kevin Camphausen
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, CRC, Bethesda, MD 20892, USA; (W.J.); (U.S.); (M.S.); (K.C.)
| | - Andra V. Krauze
- Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, 9000 Rockville Pike, Building 10, CRC, Bethesda, MD 20892, USA; (W.J.); (U.S.); (M.S.); (K.C.)
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3
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Abstract
Preeclampsia is a medical condition affecting 5-10% of pregnancies. It has serious effects on the health of the pregnant mother and developing fetus. While possible causes of preeclampsia are speculated, there is no consensus on its etiology. The advancement of big data and high-throughput technologies enables to study preeclampsia at the new and systematic level. In this review, we first highlight the recent progress made in the field of preeclampsia research using various omics technology platforms, including epigenetics, genome-wide association studies (GWAS), transcriptomics, proteomics and metabolomics. Next, we integrate the results in individual omic level studies, and show that despite the lack of coherent biomarkers in all omics studies, inhibin is a potential preeclamptic biomarker supported by GWAS, transcriptomics and DNA methylation evidence. Using network analysis on the biomarkers of all the literature reviewed here, we identify four striking sub-networks with clear biological functions supported by previous molecular-biology and clinical observations. In summary, omics integration approach offers the promise to understand molecular mechanisms in preeclampsia.
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4
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Franco-Martínez L, Martínez-Subiela S, Cerón JJ, Tecles F, Eckersall PD, Oravcova K, Tvarijonaviciute A. Biomarkers of health and welfare: A One Health perspective from the laboratory side. Res Vet Sci 2019; 128:299-307. [PMID: 31869596 DOI: 10.1016/j.rvsc.2019.12.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 11/22/2019] [Accepted: 12/10/2019] [Indexed: 10/25/2022]
Abstract
A biomarker is any measurement reflecting an interaction between a biological system and a potential hazard, which may be chemical, physical, or biological. The One World, One Health concept established that human and animal health and the environmental state are highly interconnected, sharing common aspects that can be applied globally in these three components. In this paper, we review how the concept of One Health can be applied to biomarkers of health and welfare, with a special focus on five points that can be applied to any biomarker when it is expected to be used to evaluate the human, animal or environmental health. Three of these points are: (1) the different biomarkers that can be used, (2) the different sample types where the biomarkers can be analysed, and (3) the main methods that can be used for their measurement. In addition, we will evaluate two key points needed for adequate use of a biomarker in any situation: (4) a proper analytical validation in the sample that it is going to be used, and (5) a correct selection of the biomarker. It is expected that this knowledge will help to have a broader idea about the use of biomarkers of health and welfare and also will contribute to a better and more accurate use of these biomarkers having in mind their One Health perspective.
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Affiliation(s)
- Lorena Franco-Martínez
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - Silvia Martínez-Subiela
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - José Joaquín Cerón
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - Fernando Tecles
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
| | - Peter David Eckersall
- Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, UK.
| | - Katarina Oravcova
- Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Bearsden Rd, Glasgow G61 1QH, UK.
| | - Asta Tvarijonaviciute
- Interdisciplinary Laboratory of Clinical Analysis (Interlab-UMU), Veterinary School, Campus of Excellence Mare Nostrum, University of Murcia, Espinardo, 30100 Murcia, Spain.
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5
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Prodan Žitnik I, Černe D, Mancini I, Simi L, Pazzagli M, Di Resta C, Podgornik H, Repič Lampret B, Trebušak Podkrajšek K, Sipeky C, van Schaik R, Brandslund I, Vermeersch P, Schwab M, Marc J. Personalized laboratory medicine: a patient-centered future approach. Clin Chem Lab Med 2019; 56:1981-1991. [PMID: 29990304 DOI: 10.1515/cclm-2018-0181] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 05/11/2018] [Indexed: 12/12/2022]
Abstract
In contrast to population-based medical decision making, which emphasizes the use of evidence-based treatment strategies for groups of patients, personalized medicine is based on optimizing treatment at the level of the individual patient. The creation of molecular profiles of individual patients was made possible by the advent of "omics" technologies, based on high throughput instrumental techniques in combination with biostatistics tools and artificial intelligence. The goal of personalized laboratory medicine is to use advanced technologies in the process of preventive, curative or palliative patient management. Personalized medicine does not rely on changes in concentration of a single molecular marker to make a therapeutic decision, but rather on changes of a profile of markers characterizing an individual patient's status, taking into account not only the expected response to treatment of the disease but also the expected response of the patient. Such medical approach promises a more effective diagnostics with more effective and safer treatment, as well as faster recovery and restoration of health and improved cost effectiveness. The laboratory medicine profession is aware of its key role in personalized medicine, but to empower the laboratories, at least an enhancement in cooperation between disciplines within laboratory medicine will be necessary.
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Affiliation(s)
| | - Darko Černe
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
| | - Irene Mancini
- Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Lisa Simi
- Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Mario Pazzagli
- Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy
| | - Chiara Di Resta
- Vita-Salute San Raffaele University and Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Helena Podgornik
- Department of Hematology, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Barbka Repič Lampret
- Unit for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia
| | - Katarina Trebušak Podkrajšek
- Unit for Special Laboratory Diagnostics, University Children's Hospital, University Medical Centre Ljubljana, Ljubljana, Slovenia.,Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
| | - Csilla Sipeky
- Institute of Biomedicine, University of Turku, Turku, Finland
| | - Ron van Schaik
- Department of Clinical Chemistry, Erasmus Medical Center, Rotterdam, TheNetherlands
| | - Ivan Brandslund
- Biochemistry Department, University of Southern Denmark and Vejle Hospital, Vejle, Denmark
| | | | - Matthias Schwab
- Department of Clinical Pharmacology, University Hospital Tuebingen, Tuebingen, Germany.,Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany.,Department of Pharmacy and Biochemistry, University of Tuebingen, Tuebingen, Germany
| | - Janja Marc
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
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6
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Critselis E. Impact of the General Data Protection Regulation on Clinical Proteomics Research. Proteomics Clin Appl 2019; 13:e1800199. [PMID: 30706988 DOI: 10.1002/prca.201800199] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/27/2019] [Indexed: 12/11/2022]
Abstract
The recently implemented General Data Protection Regulation (GDPR) has promising attributes for ensuring the protection of personal data collected and processed for clinical proteomic investigations. However, there exist ever increasing alarming concerns regarding its implications upon the future of clinical proteomics research both within and beyond the European Union. The main issues of concern regard GDPR legislative requirements for informed consent for study subjects' data collection and processing, data anonymization, and data storage and/or sharing, particularly in research areas which readily utilize databanks and biobanks, such as clinical proteomics investigations. The potential impacts of the aforementioned issues upon on-going and future clinical proteomics investigations are detailed, whilst recommendations for potentially resolving these emerging issues are proposed. Consensus between government, legislative, and research stakeholders, as well as impact assessments of final measures to be applied for medical research, is necessary so as to ensure the favorable perpetuation of clinical proteomics investigations and subsequent impact upon optimal patient health.
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Affiliation(s)
- Elena Critselis
- Proteomics Facility, Center for Systems Biology, Biomedical Research Foundation of the Academy of Athens, Athens, 11527, Greece
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7
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Vlahou A. Implementation of Clinical Proteomics: A Step Closer to Personalized Medicine? Proteomics Clin Appl 2018; 13:e1800088. [DOI: 10.1002/prca.201800088] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2018] [Revised: 11/23/2018] [Indexed: 01/19/2023]
Affiliation(s)
- Antonia Vlahou
- Biomedical Research FoundationAcademy of Athens Soranou Efessiou 4 11527 Athens Greece
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8
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Cominetti O, Núñez Galindo A, Corthésy J, Valsesia A, Irincheeva I, Kussmann M, Saris WHM, Astrup A, McPherson R, Harper ME, Dent R, Hager J, Dayon L. Obesity shows preserved plasma proteome in large independent clinical cohorts. Sci Rep 2018; 8:16981. [PMID: 30451909 PMCID: PMC6242904 DOI: 10.1038/s41598-018-35321-7] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 11/02/2018] [Indexed: 12/21/2022] Open
Abstract
Holistic human proteome maps are expected to complement comprehensive profile assessment of health and disease phenotypes. However, methodologies to analyze proteomes in human tissue or body fluid samples at relevant scale and performance are still limited in clinical research. Their deployment and demonstration in large enough human populations are even sparser. In the present study, we have characterized and compared the plasma proteomes of two large independent cohorts of obese and overweight individuals using shotgun mass spectrometry (MS)-based proteomics. Herein, we showed, in both populations from different continents of about 500 individuals each, the concordance of plasma protein MS measurements in terms of variability, gender-specificity, and age-relationship. Additionally, we replicated several known and new associations between proteins, clinical and molecular variables, such as insulin and glucose concentrations. In conclusion, our MS-based analyses of plasma samples from independent human cohorts proved the practical feasibility and efficiency of a large and unified discovery/replication approach in proteomics, which was also recently coined “rectangular” design.
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Affiliation(s)
- Ornella Cominetti
- Proteomics, Nestlé Institute of Health Sciences, Lausanne, Switzerland
| | | | - John Corthésy
- Proteomics, Nestlé Institute of Health Sciences, Lausanne, Switzerland.,Nutrition Analytics, Nestlé Institute of Health Sciences, Lausanne, Switzerland
| | - Armand Valsesia
- Nutrition and Metabolic Health, Nestlé Institute of Health Sciences, Lausanne, Switzerland
| | - Irina Irincheeva
- Nutrition and Metabolic Health, Nestlé Institute of Health Sciences, Lausanne, Switzerland.,Clinical Trial Unit, University of Bern, Bern, Switzerland
| | - Martin Kussmann
- Proteomics, Nestlé Institute of Health Sciences, Lausanne, Switzerland.,The Liggins Institute, University of Auckland, Auckland, New Zealand
| | - Wim H M Saris
- NUTRIM, School for Nutrition, Toxicology and Metabolism, Department of Human Biology, Maastricht University Medical Centre, Maastricht, The Netherlands
| | - Arne Astrup
- Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark
| | - Ruth McPherson
- Ruddy Canadian Cardiovascular Genetics Centre, University of Ottawa Heart Institute, Ottawa, Canada
| | - Mary-Ellen Harper
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
| | - Robert Dent
- Ottawa Hospital Weight Management Clinic, The Ottawa Hospital, Ottawa, Canada
| | - Jörg Hager
- Nutrition and Metabolic Health, Nestlé Institute of Health Sciences, Lausanne, Switzerland
| | - Loïc Dayon
- Proteomics, Nestlé Institute of Health Sciences, Lausanne, Switzerland.
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9
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Frantzi M, Latosinska A, Belczacka I, Mischak H. Urinary proteomic biomarkers in oncology: ready for implementation? Expert Rev Proteomics 2018; 16:49-63. [PMID: 30412678 DOI: 10.1080/14789450.2018.1547193] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Introduction: Biomarkers are expected to improve the management of cancer patients by enabling early detection and prediction of therapeutic response. Proteins reflect a molecular phenotype, have high potential as biomarkers, and also are key targets for intervention. Given the ease of collection and proximity to certain tumors, the urinary proteome is a rich source of biomarkers and several proteins have been already implemented. Areas covered: We examined the literature on urine proteins and proteome analysis in oncology from reports published during the last 5 years to generate an overview on the status of urine protein and peptide biomarkers, with emphasis on their actual clinical value. Expert commentary: A few studies report on biomarkers that are ready to be implemented in patient management, among others in bladder cancer and cholangiocarcinoma. These reports are based on multi-marker approaches. A high number of biomarkers, though, has been described in studies with low statistical power. In fact, several of them have been consistently reported across different studies. The latter should be the focus of attention and be tested in properly designed confirmatory and ultimately, prospective investigations. It is expected that multi-marker classifiers for a specific context-of-use, will be the preferred path toward clinical implementation.
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Affiliation(s)
- Maria Frantzi
- a Research and Development , Mosaiques Diagnostics GmbH , Hannover , Germany
| | | | - Iwona Belczacka
- a Research and Development , Mosaiques Diagnostics GmbH , Hannover , Germany
| | - Harald Mischak
- a Research and Development , Mosaiques Diagnostics GmbH , Hannover , Germany
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10
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Frantzi M, Latosinska A, Kontostathi G, Mischak H. Clinical Proteomics: Closing the Gap from Discovery to Implementation. Proteomics 2018; 18:e1700463. [PMID: 29785737 DOI: 10.1002/pmic.201700463] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2018] [Revised: 05/10/2018] [Indexed: 12/15/2022]
Abstract
Clinical proteomics, the application of proteome analysis to serve a clinical purpose, represents a major field in the area of proteome research. Over 1000 manuscripts on this topic are published each year, with numbers continuously increasing. However, the anticipated outcome, the transformation of the reported findings into improvements in patient management, is not immediately evident. In this article, the value and validity of selected clinical proteomics findings are investigated, and it is assessed how far implementation has progressed. A main conclusion from this assessment is that to achieve implementation, well-powered clinical studies are required in the appropriate population, addressing a specific clinical need and with a clear context-of-use. Efforts toward implementation, to be feasible, must be supported by the key players in science: publishers and funders. The authors propose a change on objectives, from additional discovery studies toward studies aiming at validation of the plethora of potential biomarkers that have been described, to demonstrate practical value of clinical proteomics. All elements required, potential biomarkers, technologies, and bio-banked samples are available (based on today's literature), hence a change in focus from discovery toward validation and application is not only urgently necessary, but also possible based on resources available today.
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Affiliation(s)
- Maria Frantzi
- Mosaiques Diagnostics GmbH, Hannover, 30659, Germany
| | | | - Georgia Kontostathi
- Department of Biotechnology, Biomedical Research Foundation Academy of Athens, Athens, 11527, Greece
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11
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Atay S, Wilkey DW, Milhem M, Merchant M, Godwin AK. Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers. Mol Cell Proteomics 2017; 17:495-515. [PMID: 29242380 DOI: 10.1074/mcp.ra117.000267] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2017] [Revised: 10/21/2017] [Indexed: 12/13/2022] Open
Abstract
Developing tumors continuously release nano-sized vesicles that represent circulating "fingerprints" of the tumor's identity. In gastrointestinal stromal tumor (GIST), we have previously reported that these tumors release "oncosomes" carrying the constitutively activated tyrosine kinase (TK) receptor KIT. Despite the clinical utility of TK inhibitors, such as imatinib mesylate (IM), recurrence and metastasis are clinical problems that urge the need to identify new tumor-derived molecules. To this aim, we performed the first high quality proteomic study of GIST-derived exosomes (GDEs) and identified 1,060 proteins composing the core GDE proteome (cGDEp). The cGDEp was enriched in diagnostic markers (e.g. KIT, CD34, ANO1, PROM1, PRKCQ, and ENG), as well as proteins encoded by genes previously reported expressed in GIST (e.g. DPP4, FHL1, CDH11, and KCTD12). Many of these proteins were validated using cell lines, patient-derived KIT+ exosomes, and GIST tissues. We further show that in vitro and in vivo-derived GDE, carry proteins associated with IM response, such as Sprouty homolog 4 (SPRY4), surfeit 4 (SURF4), ALIX, and the cGMP-dependent 3',5'-cyclic phosphodiesterase 2A (PDE2A). Additionally, we report that the total exosome levels and exosome-associated KIT and SPRY4 protein levels have therapeutic values. In fact, molecular characterization of in vivo-derived KIT+ exosomes indicate significant sorting of p-KITTyr719, total KIT, and SPRY4 after IM-treatment of metastatic patients as compared with the pre-IM levels. Our data suggest that analysis of circulating exosomes levels and molecular markers of IM response in GIST patients with primary and metastatic disease is suitable to develop liquid based biopsies for the diagnosis, prognosis, and monitoring of response to treatment of these tumors. In summary, these findings provide the first insight into the proteome of GIST-derived oncosomes and offers a unique opportunity to further understand their oncogenic elements which contribute to tumorigenesis and drug resistance. Data are available via ProteomeXchange with identifier PXD007997.
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Affiliation(s)
- Safinur Atay
- From the ‡Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., 4005 WHE, MS3040, Kansas City, Kansas 66160;
| | - Daniel W Wilkey
- §University of Louisville Room 209, Donald Baxter Research Building, 570 S. Preston Street, Louisville, Kentucky 40202
| | - Mohammed Milhem
- ¶Division of Hematology, Oncology, Blood and Marrow Transplantation 200 Hawkins Drive, C32 GH Iowa City, Iowa 52242
| | - Michael Merchant
- §University of Louisville Room 209, Donald Baxter Research Building, 570 S. Preston Street, Louisville, Kentucky 40202
| | - Andrew K Godwin
- From the ‡Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd., 4005 WHE, MS3040, Kansas City, Kansas 66160.,‖University of Kansas Cancer Center, 3901 Rainbow Blvd., 4005 WHE, MS3040, Kansas City, Kansas 66160
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12
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Lipworth W, Mason PH, Kerridge I, Ioannidis JPA. Ethics and Epistemology in Big Data Research. JOURNAL OF BIOETHICAL INQUIRY 2017; 14:489-500. [PMID: 28321561 DOI: 10.1007/s11673-017-9771-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2016] [Accepted: 01/17/2017] [Indexed: 06/06/2023]
Abstract
Biomedical innovation and translation are increasingly emphasizing research using "big data." The hope is that big data methods will both speed up research and make its results more applicable to "real-world" patients and health services. While big data research has been embraced by scientists, politicians, industry, and the public, numerous ethical, organizational, and technical/methodological concerns have also been raised. With respect to technical and methodological concerns, there is a view that these will be resolved through sophisticated information technologies, predictive algorithms, and data analysis techniques. While such advances will likely go some way towards resolving technical and methodological issues, we believe that the epistemological issues raised by big data research have important ethical implications and raise questions about the very possibility of big data research achieving its goals.
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Affiliation(s)
- Wendy Lipworth
- Centre for Values, Ethics and the Law in Medicine, University of Sydney, Medical Foundation Building (K25), Sydney, NSW, 2006, Australia.
| | - Paul H Mason
- Centre for Values, Ethics and the Law in Medicine, University of Sydney, Medical Foundation Building (K25), Sydney, NSW, 2006, Australia
| | - Ian Kerridge
- Centre for Values, Ethics and the Law in Medicine, University of Sydney, Medical Foundation Building (K25), Sydney, NSW, 2006, Australia
- Haematology Department, Royal North Shore Hospital, Reserve Rd, St Leonards, NSW, 2065, Australia
| | - John P A Ioannidis
- Stanford University School of Medicine, Stanford, CA, USA
- Stanford University School of Humanities and Sciences, Stanford, CA, USA
- Meta-Research Innovation Center at Stanford, Stanford, CA, USA
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13
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Abstract
Research efforts targeting the identification of bladder cancer biomarkers have been extensive during the past decade. Investigations have been performed at the genome, transcriptome, proteome, and metabolome levels and outputs have started appearing including the sketching of disease molecular subtypes. Proteins are directly linked to cell phenotype hence they accumulate special interest as both biomarkers and therapeutic targets. Multiple technical challenges exist, of the main, being the protein concentration vast dynamic range and presence of proteins in modified forms. The scope of this review is to summarize the contribution of proteomics research in this quest of bladder cancer biomarkers. To obtain an unbiased and comprehensive overview, the scientific literature was searched for manuscripts describing proteomic studies on urothelial cancer from the last ten years and those including independent verification studies in urine, tissue and blood are briefly presented. General observations include: a) in most cases, suboptimal experimental design including healthy controls in biomarker discovery and frequently biomarker verification, is followed; b) variability in protein findings between studies can be observed, to some extent reflecting complexity of experimental approaches and proteome itself; c) consistently reported biomarkers include mainly plasma proteins and d) compilation of protein markers into diagnostic panels appears the most promising way forward. Two main avenues of research can now be foreseen: targeting integration of the existing disparate data with proteomic findings being placed in the context of existing knowledge on bladder cancer subtypes and in parallel, accumulation of clinical samples to support proper validation studies of promising marker combinations.
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Affiliation(s)
| | - Antonia Vlahou
- Biomedical Research Foundation Academy of Athens , Biotechnology Division, Athens, Greece
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14
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Nkuipou-Kenfack E, Zürbig P, Mischak H. The long path towards implementation of clinical proteomics: Exemplified based on CKD273. Proteomics Clin Appl 2017; 11. [DOI: 10.1002/prca.201600104] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2016] [Revised: 11/28/2016] [Accepted: 12/22/2016] [Indexed: 12/26/2022]
Affiliation(s)
| | | | - Harald Mischak
- Mosaiques Diagnostics GmbH; Hannover Germany
- BHF Glasgow Cardiovascular Research Centre; University of Glasgow; Glasgow United Kingdom
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15
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Mokou M, Lygirou V, Vlahou A, Mischak H. Proteomics in cardiovascular disease: recent progress and clinical implication and implementation. Expert Rev Proteomics 2017; 14:117-136. [DOI: 10.1080/14789450.2017.1274653] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Marika Mokou
- Biotechnology Division, Biomedical Research Foundation Academy of Athens, Athens, Greece
| | - Vasiliki Lygirou
- Biotechnology Division, Biomedical Research Foundation Academy of Athens, Athens, Greece
| | - Antonia Vlahou
- Biotechnology Division, Biomedical Research Foundation Academy of Athens, Athens, Greece
| | - Harald Mischak
- Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK
- Mosaiques Diagnostics, Hannover, Germany
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16
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The limitations of opportunistic epidemiology, pseudopod epidemiology. Eur J Epidemiol 2016; 31:957-966. [DOI: 10.1007/s10654-016-0196-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2016] [Accepted: 08/31/2016] [Indexed: 12/20/2022]
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17
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López de Maturana E, Pineda S, Brand A, Van Steen K, Malats N. Toward the integration of Omics data in epidemiological studies: still a "long and winding road". Genet Epidemiol 2016; 40:558-569. [PMID: 27432111 DOI: 10.1002/gepi.21992] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2015] [Revised: 05/22/2016] [Accepted: 06/05/2016] [Indexed: 12/23/2022]
Abstract
Primary and secondary prevention can highly benefit a personalized medicine approach through the accurate discrimination of individuals at high risk of developing a specific disease from those at moderate and low risk. To this end precise risk prediction models need to be built. This endeavor requires a precise characterization of the individual exposome, genome, and phenome. Massive molecular omics data representing the different layers of the biological processes of the host and the nonhost will enable to build more accurate risk prediction models. Epidemiologists aim to integrate omics data along with important information coming from other sources (questionnaires, candidate markers) that has been proved to be relevant in the discrimination risk assessment of complex diseases. However, the integrative models in large-scale epidemiologic research are still in their infancy and they face numerous challenges, some of them at the analytical stage. So far, there are a small number of studies that have integrated more than two omics data sets, and the inclusion of non-omics data in the same models is still missing in most of studies. In this contribution, we aim at approaching the omics and non-omics data integration from the epidemiology scope by considering the "massive" inclusion of variables in the risk assessment and predictive models. We also provide already available examples of integrative contributions in the field, propose analytical strategies that allow considering both omics and non-omics data in the models, and finally review the challenges imbedding this type of research.
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Affiliation(s)
| | - Sílvia Pineda
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain
| | - Angela Brand
- Institute for Public Health Genomics, Maastricht University, Maastricht, Netherlands
| | - Kristel Van Steen
- Laboratory of Biostatistics, Biomedicine and Bioinformatics, GIGA, University of Liège, Belgium
| | - Núria Malats
- Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
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18
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Abstract
Autoantibodies are a key component for the diagnosis, prognosis and monitoring of various diseases. In order to discover novel autoantibody targets, highly multiplexed assays based on antigen arrays hold a great potential and provide possibilities to analyze hundreds of body fluid samples for their reactivity pattern against thousands of antigens in parallel. Here, we provide an overview of the available technologies for producing antigen arrays, highlight some of the technical and methodological considerations and discuss their applications as discovery tools. Together with recent studies utilizing antigen arrays, we give an overview on how the different types of antigen arrays have and will continue to deliver novel insights into autoimmune diseases among several others.
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19
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Gwinner W, Metzger J, Husi H, Marx D. Proteomics for rejection diagnosis in renal transplant patients: Where are we now? World J Transplant 2016; 6:28-41. [PMID: 27011903 PMCID: PMC4801803 DOI: 10.5500/wjt.v6.i1.28] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2015] [Revised: 12/14/2015] [Accepted: 01/05/2016] [Indexed: 02/05/2023] Open
Abstract
Rejection is one of the key factors that determine the long-term allograft function and survival in renal transplant patients. Reliable and timely diagnosis is important to treat rejection as early as possible. Allograft biopsies are not suitable for continuous monitoring of rejection. Thus, there is an unmet need for non-invasive methods to diagnose acute and chronic rejection. Proteomics in urine and blood samples has been explored for this purpose in 29 studies conducted since 2003. This review describes the different proteomic approaches and summarizes the results from the studies that examined proteomics for the rejection diagnoses. The potential limitations and open questions in establishing proteomic markers for rejection are discussed, including ongoing trials and future challenges to this topic.
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20
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Implementation of CE-MS-identified proteome-based biomarker panels in drug development and patient management. Bioanalysis 2016; 8:439-55. [DOI: 10.4155/bio.16.8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
The recent advancements in clinical proteomics enabled identification of biomarker panels for a large range of diseases. A number of CE-MS-identified biomarker panels were verified and implemented in clinical studies. Despite multiple challenges, accumulating evidence supports the value and the need for proteome-based biomarker panels. In this perspective, we provide an overview of clinical studies indicating the added value of CE-MS biomarker panels over traditional diagnostics and monitoring methods. We outline apparent advantages of applying novel proteomic biomarker panels for disease diagnosis, prognosis, staging, drug development and patient management. Facing the plethora of benefits associated with the use of CE-MS biomarker panels, we envision their implementation into the medical practice in the near future.
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21
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Khoury MJ. Planning for the Future of Epidemiology in the Era of Big Data and Precision Medicine. Am J Epidemiol 2015; 182:977-9. [PMID: 26628513 DOI: 10.1093/aje/kwv228] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 08/19/2015] [Indexed: 01/10/2023] Open
Abstract
We live in the era of genomics and big data. Evaluating the impact on health of large-scale biological, social, and environmental data is an emerging challenge in the field of epidemiology. In the past 3 years, major discussions and plans for the future of epidemiology, including with several recommendations for actions to transform the field, have been launched by 2 institutes within the National Institutes of Health. In the present commentary, I briefly explore the themes of these recommendations and their effects on leadership, resources, cohort infrastructure, and training. Ongoing engagement within the epidemiology community is needed to determine how to shape the evolution of the field and what truly matters for changing population health. We also need to assess how to leverage existing epidemiology resources and develop new studies to improve human health. Readers are invited to examine these recommendations, consider others that might be important, and join in the conversation about the future of epidemiology.
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22
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Fredolini C, Byström S, Pin E, Edfors F, Tamburro D, Iglesias MJ, Häggmark A, Hong MG, Uhlen M, Nilsson P, Schwenk JM. Immunocapture strategies in translational proteomics. Expert Rev Proteomics 2015; 13:83-98. [PMID: 26558424 PMCID: PMC4732419 DOI: 10.1586/14789450.2016.1111141] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Aiming at clinical studies of human diseases, antibody-assisted assays have been applied to biomarker discovery and toward a streamlined translation from patient profiling to assays supporting personalized treatments. In recent years, integrated strategies to couple and combine antibodies with mass spectrometry-based proteomic efforts have emerged, allowing for novel possibilities in basic and clinical research. Described in this review are some of the field's current and emerging immunocapture approaches from an affinity proteomics perspective. Discussed are some of their advantages, pitfalls and opportunities for the next phase in clinical and translational proteomics.
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Affiliation(s)
- Claudia Fredolini
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Sanna Byström
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Elisa Pin
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Fredrik Edfors
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Davide Tamburro
- Department of Oncology-Pathology, Clinical Proteomics Mass Spectrometry, SciLifeLab, Karolinska Institutet, Solna, Sweden
| | - Maria Jesus Iglesias
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Anna Häggmark
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Mun-Gwan Hong
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Mathias Uhlen
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Peter Nilsson
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
| | - Jochen M Schwenk
- Affinity Proteomics, SciLifeLab, School of Biotechnology, KTH - Royal Institute of Technology, Solna, Sweden
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23
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Frantzi M, Latosinska A, Merseburger AS, Mischak H. Recent progress in urinary proteome analysis for prostate cancer diagnosis and management. Expert Rev Mol Diagn 2015; 15:1539-54. [PMID: 26491818 DOI: 10.1586/14737159.2015.1104248] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Prostate cancer (PCa) is fifth leading cause of cancer-associated deaths in men worldwide. Although the application of the serum prostate-specific antigen (PSA) screening test resulted in an increase in the PCa diagnosed cases, it demonstrated a negligible benefit regarding the associated mortality. Treatment options vary, with active surveillance to be preferable for patients with low-risk PCa and therapy of advanced castration-resistant PCa to rely on α-emitters and cytotoxic chemotherapy. Although recent developments have led to the approval of novel drugs for the treatment of castration-resistant PCa, the optimal sequence and timing of medication have not been yet determined. New screening modalities could improve the discriminatory accuracy between tumors with favorable clinical prognosis. Implementation of proteomic-based biomarkers appears to be a promising improvement, which could enable a more accurate diagnosis, guide treatment and improve patient outcome. Reviewed here are urinary proteome-based approaches for detection of PCa and patient management.
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Affiliation(s)
- Maria Frantzi
- a Mosaiques diagnostics GmbH , Hannover , Germany.,b Biotechnology Division , Biomedical Research Foundation Academy of Athens , Athens , Greece
| | - Agnieszka Latosinska
- b Biotechnology Division , Biomedical Research Foundation Academy of Athens , Athens , Greece
| | | | - Harald Mischak
- a Mosaiques diagnostics GmbH , Hannover , Germany.,d Institute of Cardiovascular and Medical Sciences , University of Glasgow , Glasgow , UK
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24
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Conley YP, Heitkemper M, McCarthy D, Anderson CM, Corwin EJ, Daack-Hirsch S, Dorsey SG, Gregory KE, Groer MW, Henly SJ, Landers T, Lyon DE, Taylor JY, Voss J. Educating future nursing scientists: Recommendations for integrating omics content in PhD programs. Nurs Outlook 2015; 63:417-27. [PMID: 26123776 PMCID: PMC7849773 DOI: 10.1016/j.outlook.2015.06.006] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 06/05/2015] [Accepted: 06/08/2015] [Indexed: 01/06/2023]
Abstract
Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science's Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals.
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Affiliation(s)
- Yvette P Conley
- School of Nursing, University of Pittsburgh, Pittsburgh, PA.
| | | | | | | | | | | | - Susan G Dorsey
- School of Nursing, University of Maryland, Baltimore, MD
| | | | | | - Susan J Henly
- School of Nursing, University of Minnesota, Minneapolis, MN
| | | | - Debra E Lyon
- College of Nursing, University of Florida, Gainesville, FL
| | | | - Joachim Voss
- School of Nursing, University of Washington, Seattle, WA
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25
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Frantzi M, Latosinska A, Flühe L, Hupe MC, Critselis E, Kramer MW, Merseburger AS, Mischak H, Vlahou A. Developing proteomic biomarkers for bladder cancer: towards clinical application. Nat Rev Urol 2015; 12:317-30. [PMID: 26032553 DOI: 10.1038/nrurol.2015.100] [Citation(s) in RCA: 63] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Clinical use of proteomic biomarkers has the potential to substantially improve the outcomes of patients with bladder cancer. An unmet clinical need evidently exists for noninvasive biomarkers, which might enable improvements in both the diagnosis and prognosis of patients with bladder cancer, as well as improved monitoring of patients for the presence of recurrence. Urine is considered the optimal noninvasive source of proteomic biomarkers in patients with bladder cancer. Currently, a number of single-protein biomarkers have been detected in urine and tissue using a variety of proteomic techniques, each having specific conceptual considerations and technical implications. Promising preclinical data are available for several of these proteins; however, the combination of single urinary proteins into multimarker panels might better encompass the molecular heterogeneity of bladder cancer within this patient population, and prove more effective in clinical use.
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Affiliation(s)
- Maria Frantzi
- Biotechnology Division, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece
| | - Agnieszka Latosinska
- Biotechnology Division, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece
| | - Leif Flühe
- Mosaiques Diagnostics GmbH, Rotenburger Strasse 20, 30659 Hannover, Germany
| | - Marie C Hupe
- Department of Urology and Urological Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
| | - Elena Critselis
- Biotechnology Division, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece
| | - Mario W Kramer
- Department of Urology and Urological Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
| | - Axel S Merseburger
- Department of Urology and Urological Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany
| | - Harald Mischak
- BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Avenue, Glasgow G12 8TA, UK
| | - Antonia Vlahou
- Biotechnology Division, Biomedical Research Foundation Academy of Athens, 4 Soranou Ephessiou Street, 115 27 Athens, Greece
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