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Cancers Aug 2023Cancer is the leading cause of death worldwide, with the most frequent being breast cancer in women, prostate cancer in men and colon cancer in both sexes. The use of... (Review)
Review
INTRODUCTION
Cancer is the leading cause of death worldwide, with the most frequent being breast cancer in women, prostate cancer in men and colon cancer in both sexes. The use of metabolomics to find new biomarkers can provide knowledge about possible interventions based on the presence of oncometabolites in different cancer types.
OBJECTIVES
The primary purpose of this review is to analyze the characteristic metabolome of three of the most frequent cancer types. We further want to identify the existence and success rate of metabolomics-based intervention in patients suffering from those cancer types. Our conclusions are based on the analysis of the methodological quality of the studies.
METHODS
We searched for studies that investigated the metabolomic characteristics in patients suffering from breast cancer, prostate cancer or colon cancer in clinical trials. The data were analyzed, as well as the effects of specific interventions based on identified metabolomics and one or more oncometabolites. The used databases were PubMed, Virtual Health Library, Web of Science, EBSCO and Cochrane Library. Only nine studies met the selection criteria. Study bias was analyzed using the Cochrane risk of bias tool. This systematic review protocol was registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42023401474).
RESULTS
Only nine studies about clinical trials were included in this review and show a moderate quality of evidence. Metabolomics-based interventions related with disease outcome were conflictive with no or small changes in the metabolic characteristics of the different cancer types.
CONCLUSIONS
This systematic review shows some interesting results related with metabolomics-based interventions and their effects on changes in certain cancer oncometabolites. The small number of studies we identified which fulfilled our inclusion criteria in this systematic review does not allow us to draw definitive conclusions. Nevertheless, some results can be considered as promising although further research is needed. That research must focus not only on the presence of possible oncometabolites but also on possible metabolomics-based interventions and their influence on the outcome in patients suffering from breast cancer, prostate cancer or colon cancer.
PubMed: 37686573
DOI: 10.3390/cancers15174297 -
Seminars in Arthritis and Rheumatism Apr 2023Osteoarthritis (OA) is a joint disease that is clinically diagnosed using components of history, physical exam, and characteristic radiographic findings, such as joint... (Review)
Review
PURPOSE
Osteoarthritis (OA) is a joint disease that is clinically diagnosed using components of history, physical exam, and characteristic radiographic findings, such as joint space narrowing. Currently, there are no laboratory findings that are specific to a diagnosis of OA. The purpose of this systematic review is to evaluate the state of current studies of metabolomic biomarkers that can aid in the diagnosis and treatment of OA.
METHODS
Articles were gathered from PubMed and Web of Science using the search terms "osteoarthritis" and "biomarkers" and "metabolomics". Last search of databases took place December 3rd, 2022. Duplicates were manually screened, along with any other results that were not original journal articles. Only original reports involving populations with diagnosed primary or secondary OA (human participants) or surgically induced OA (animal participants) and a healthy control group for comparison were considered for inclusion. Metabolites and metabolic pathways reported in included articles were then manually extracted and evaluated for importance based on reported a priori p-values and/or area under the receiver-operator curve (AUC).
RESULTS
Of the 161 results that were returned in the database searches, 43 unique articles met the inclusion criteria. Articles were categorized based on body fluid analyzed: 6 studies on urine samples, 13 studies on plasma samples, 11 studies on synovial fluid (SF) samples, 11 studies on serum samples, 1 study on both synovial fluid and serum, and 1 study that involved both plasma and synovial fluid. To synthesize results, individual metabolites, as well as metabolic pathways that involve frequently reported metabolites, are presented for each study. Indications as to whether metabolite levels were increased or decreased are also included if this data was included in the original articles.
CONCLUSIONS
These studies clearly show that there are a wide range of metabolic pathways perturbed in OA. For this period, there was no consensus on a single metabolite, or panel of metabolites, that would be clinically useful in early diagnosis of OA or distinguishing OA from a healthy control. However, many common metabolic pathways were identified in the studies, including TCA cycle, fatty acid metabolism, amino acid metabolism (notably BCAA metabolism and tryptophan metabolism via kynurenine pathway), nucleotide metabolism, urea cycle, cartilage matrix components, and phospholipid metabolism. Future research is needed to define effective clinical biomarkers of osteoarthritis from metabolomic and other data.
Topics: Animals; Humans; Osteoarthritis; Metabolomics; Biomarkers; Synovial Fluid; Metabolic Networks and Pathways
PubMed: 36736024
DOI: 10.1016/j.semarthrit.2023.152163 -
Environment International Jun 2022Systematic evidence maps are increasingly used to develop chemical risk assessments. These maps can provide an overview of available studies and relevant study... (Review)
Review
BACKGROUND
Systematic evidence maps are increasingly used to develop chemical risk assessments. These maps can provide an overview of available studies and relevant study information to be used for various research objectives and applications. Environmental epidemiological studies that examine the impact of chemical exposures on various 'omic profiles in human populations provide relevant mechanistic information and can be used for benchmark dose modeling to derive potential human health reference values.
OBJECTIVES
To create a systematic evidence map of environmental epidemiological studies examining environmental contaminant exposures with 'omics in order to characterize the extent of available studies for future research needs.
METHODS
Systematic review methods were used to search and screen the literature and included the use of machine learning methods to facilitate screening studies. The Populations, Exposures, Comparators and Outcomes (PECO) criteria were developed to identify and screen relevant studies. Studies that met the PECO criteria after full-text review were summarized with information such as study population, study design, sample size, exposure measurement, and 'omics analysis.
RESULTS
Over 10,000 studies were identified from scientific databases. Screening processes were used to identify 84 studies considered PECO-relevant after full-text review. Various contaminants (e.g. phthalate, benzene, arsenic, etc.) were investigated in epidemiological studies that used one or more of the four 'omics of interest: epigenomics, transcriptomics, proteomics, and metabolomics . The epidemiological study designs that were used to explore single or integrated 'omic research questions with contaminant exposures were cohort studies, controlled trials, cross-sectional, and case-control studies. An interactive web-based systematic evidence map was created to display more study-related information.
CONCLUSIONS
This systematic evidence map is a novel tool to visually characterize the available environmental epidemiological studies investigating contaminants and biological effects using 'omics technology and serves as a resource for investigators and allows for a range of applications in chemical research and risk assessment needs.
Topics: Cross-Sectional Studies; Environmental Exposure; Epidemiologic Studies; Humans; Reference Values; Risk Assessment
PubMed: 35551006
DOI: 10.1016/j.envint.2022.107243 -
Diagnostics (Basel, Switzerland) Nov 2023Gastric cancer is the fourth most frequently diagnosed form of cancer and the third leading cause of cancer-related mortality worldwide. The aim of this review is to... (Review)
Review
INTRODUCTION
Gastric cancer is the fourth most frequently diagnosed form of cancer and the third leading cause of cancer-related mortality worldwide. The aim of this review is to identify individual metabolic biomarkers and their association with accurate diagnostic values, which can predict gastric cancer metastasis.
MATERIALS AND METHODS
After searching the keywords, 83 articles were found over a period of 13 years. One was eliminated because it was not written in English, and two were published outside the selected period. Seven scientific papers were qualified for this investigation after eliminating duplicates, non-related articles, systematic reviews, and restricted access studies.
RESULTS
New metabolic biomarkers with predictive value for gastric cancer metastasis and for elucidating metabolic pathways of the metastatic process have been found. The pathogenic processes can be outlined as follows: pro-oxidant capacity, T-cell inactivation, cell cycle arrest, energy production and mitochondrial enzyme impairment, cell viability and pro-apoptotic effect, enhanced degradation of collagen extracellular matrix, migration, invasion, structural protein synthesis, and tumoral angiogenesis.
CONCLUSION
Metabolic biomarkers have been recognized as independent risk factors in the molecular process of gastric cancer metastasis, with good diagnostic and prognostic value.
PubMed: 37998537
DOI: 10.3390/diagnostics13223401 -
Frontiers in Molecular Biosciences 2020Magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and the McDonald's clinical criteria are currently utilized tools in diagnosing multiple sclerosis.... (Review)
Review
BACKGROUND
Magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and the McDonald's clinical criteria are currently utilized tools in diagnosing multiple sclerosis. However, a more conclusive, consistent, and efficient way of diagnosing multiple sclerosis (MS) is yet to be discovered. A potential biomarker, discovered using advances in high-throughput sequencing such as nuclear magnetic resonance (NMR) spectroscopy and other "Omics"-based techniques, may make diagnosis and prognosis more reliable resulting in a more personalized and targeted treatment regime and improved outcomes. The aim of this review was to systematically search the literature for potential biomarkers from any bodily fluid that could consistently and accurately diagnose MS and/or indicate disease progression.
METHODS
A systematic literature review of EMBASE, PubMed (MEDLINE), The Cochrane Library, and CINAHL databases produced over a thousand potential studies. Inclusion criteria stated studies with potential biomarker outcomes for people with MS were to be included in the review. Studies were limited to those with human participants who had a clinically defined diagnosis of MS and published in English, with no limit placed on date of publication or the type of bodily fluid sampled.
RESULTS
A total of 1,805 studies were recorded from the literature search. A total of 1,760 studies were removed based on their abstract, with a further 18 removed after considering the full text. A total of 30 studies were considered relevant and had their data retrieved and analyzed. Due to the heterogeneity of focus and results from the refined studies, a narrative synthesis was favored.
CONCLUSION
Several promising candidate biomarkers suitable for clinical application in MS have been studied. It is recommended follow-up studies with larger sample sizes be completed on several potential biomarkers.
PubMed: 33381517
DOI: 10.3389/fmolb.2020.574133 -
Metabolites Dec 2022Cancers are the leading cause of death worldwide. The most common cancers include breast, lung, and colorectum. Salivary metabolome profiling is a novel non-invasive... (Review)
Review
Cancers are the leading cause of death worldwide. The most common cancers include breast, lung, and colorectum. Salivary metabolome profiling is a novel non-invasive method in oncological diagnosis. This systematic review was designed to answer the question "Are salivary metabolites reliable for the diagnosis of systemic cancers?". Following the inclusion and exclusion criteria, nineteen studies were included (according to PRISMA statement guidelines). Changes in salivary metabolome were most commonly determined in patients with breast cancer, gastrointestinal cancers, and lung cancer. Most studies involved unstimulated whole saliva as the diagnostic material, evaluated by different spectroscopic methods. Among the found saliva metabolites, the alterations in the metabolic pathways of amino acids and polyamines were most frequently observed, which showed significant predictive values in oncological diagnostics. The most frequently encountered risks of bias were the absence of data regarding blinding, sample size justification, and randomisation. In conclusion, salivary metabolites seem to be potentially reliable for detecting the most common systemic cancers. However, further research is desirable to confirm these outcomes and to detect new potential metabolic biomarkers in saliva.
PubMed: 36676953
DOI: 10.3390/metabo13010028 -
Metabolites Sep 2021Lung cancer continues to be a significant burden worldwide and remains the leading cause of cancer-associated mortality. Two considerable challenges posed by this... (Review)
Review
Lung cancer continues to be a significant burden worldwide and remains the leading cause of cancer-associated mortality. Two considerable challenges posed by this disease are the diagnosis of 61% of patients in advanced stages and the reduced five-year survival rate of around 4%. Noninvasively collected samples are gaining significant interest as new areas of knowledge are being sought and opened up. Metabolomics is one of these growing areas. In recent years, the use of metabolomics as a resource for the study of lung cancer has been growing. We conducted a systematic review of the literature from the past 10 years in order to identify some metabolites associated with lung cancer. More than 150 metabolites have been associated with lung cancer-altered metabolism. These were detected in different biological samples by different metabolomic analytical platforms. Some of the published results have been consistent, showing the presence/alteration of specific metabolites. However, there is a clear variability due to lack of a full clinical characterization of patients or standardized patients selection. In addition, few published studies have focused on the added value of the metabolomic profile as a means of predicting treatment response for lung cancer. This review reinforces the need for consistent and systematized studies, which will help make it possible to identify metabolic biomarkers and metabolic pathways responsible for the mechanisms that promote tumor progression, relapse and eventually resistance to therapy.
PubMed: 34564447
DOI: 10.3390/metabo11090630 -
Journal of Translational Medicine May 2020Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) is a complex illness that has an unknown aetiology. It has been... (Review)
Review
BACKGROUND
Chronic Fatigue Syndrome/Myalgic Encephalomyelitis/Systemic Exertion Intolerance Disease (CFS/ME/SEID) is a complex illness that has an unknown aetiology. It has been proposed that metabolomics may contribute to the illness pathogenesis of CFS/ME/SEID. In metabolomics, the systematic identification of measurable changes in small molecule metabolite products have been identified in cases of both monogenic and heterogenic diseases. Therefore, the aim of this systematic review was to evaluate if there is any evidence of metabolomics contributing to the pathogenesis of CFS/ME/SEID.
METHODS
PubMed, Scopus, EBSCOHost (Medline) and EMBASE were searched using medical subject headings terms for Chronic Fatigue Syndrome, metabolomics and metabolome to source papers published from 1994 to 2020. Inclusion and exclusion criteria were used to identify studies reporting on metabolites measured in blood and urine samples from CFS/ME/SEID patients compared with healthy controls. The Joanna Briggs Institute Checklist was used to complete a quality assessment for all the studies included in this review.
RESULTS
11 observational case control studies met the inclusion criteria for this review. The primary outcome of metabolite measurement in blood samples of CFS/ME/SEID patients was reported in ten studies. The secondary outcome of urine metabolites was measured in three of the included studies. No studies were excluded from this review based on a low-quality assessment score, however there was inconsistency in the scientific research design of the included studies. Metabolites associated with the amino acid pathway were the most commonly impaired with significant results in seven out of the 10 studies. However, no specific metabolite was consistently impaired across all of the studies. Urine metabolite results were also inconsistent.
CONCLUSION
The findings of this systematic review reports that a lack of consistency with scientific research design provides little evidence for metabolomics to be clearly defined as a contributing factor to the pathogenesis of CFS/ME/SEID. Further research using the same CFS/ME/SEID diagnostic criteria, metabolite analysis method and control of the confounding factors that influence metabolite levels are required.
Topics: Case-Control Studies; Fatigue Syndrome, Chronic; Humans; Metabolomics
PubMed: 32404171
DOI: 10.1186/s12967-020-02356-2 -
Journal of Cachexia, Sarcopenia and... Jun 2024Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for...
BACKGROUND
Proliferating cancer cells shift their metabolism towards glycolysis, even in the presence of oxygen, to especially generate glycolytic intermediates as substrates for anabolic reactions. We hypothesize that a similar metabolic remodelling occurs during skeletal muscle hypertrophy.
METHODS
We used mass spectrometry in hypertrophying C2C12 myotubes in vitro and plantaris mouse muscle in vivo and assessed metabolomic changes and the incorporation of the [U-C]glucose tracer. We performed enzyme inhibition of the key serine synthesis pathway enzyme phosphoglycerate dehydrogenase (Phgdh) for further mechanistic analysis and conducted a systematic review to align any changes in metabolomics during muscle growth with published findings. Finally, the UK Biobank was used to link the findings to population level.
RESULTS
The metabolomics analysis in myotubes revealed insulin-like growth factor-1 (IGF-1)-induced altered metabolite concentrations in anabolic pathways such as pentose phosphate (ribose-5-phosphate/ribulose-5-phosphate: +40%; P = 0.01) and serine synthesis pathway (serine: -36.8%; P = 0.009). Like the hypertrophy stimulation with IGF-1 in myotubes in vitro, the concentration of the dipeptide l-carnosine was decreased by 26.6% (P = 0.001) during skeletal muscle growth in vivo. However, phosphorylated sugar (glucose-6-phosphate, fructose-6-phosphate or glucose-1-phosphate) decreased by 32.2% (P = 0.004) in the overloaded muscle in vivo while increasing in the IGF-1-stimulated myotubes in vitro. The systematic review revealed that 10 metabolites linked to muscle hypertrophy were directly associated with glycolysis and its interconnected anabolic pathways. We demonstrated that labelled carbon from [U-C]glucose is increasingly incorporated by ~13% (P = 0.001) into the non-essential amino acids in hypertrophying myotubes, which is accompanied by an increased depletion of media serine (P = 0.006). The inhibition of Phgdh suppressed muscle protein synthesis in growing myotubes by 58.1% (P < 0.001), highlighting the importance of the serine synthesis pathway for maintaining muscle size. Utilizing data from the UK Biobank (n = 450 243), we then discerned genetic variations linked to the serine synthesis pathway (PHGDH and PSPH) and to its downstream enzyme (SHMT1), revealing their association with appendicular lean mass in humans (P < 5.0e-8).
CONCLUSIONS
Understanding the mechanisms that regulate skeletal muscle mass will help in developing effective treatments for muscle weakness. Our results provide evidence for the metabolic rewiring of glycolytic intermediates into anabolic pathways during muscle growth, such as in serine synthesis.
Topics: Glucose; Muscle, Skeletal; Animals; Mice; Humans; Hypertrophy; Muscle Fibers, Skeletal; Insulin-Like Growth Factor I; Metabolomics
PubMed: 38742477
DOI: 10.1002/jcsm.13468 -
Diagnostics (Basel, Switzerland) Feb 2019Prostate cancer (PCa) diagnosis with current biomarkers is difficult and often results in unnecessary invasive procedures as well as over-diagnosis and over-treatment,... (Review)
Review
Prostate cancer (PCa) diagnosis with current biomarkers is difficult and often results in unnecessary invasive procedures as well as over-diagnosis and over-treatment, highlighting the need for novel biomarkers. The aim of this review is to provide a summary of available metabolomics PCa biomarkers, particularly for clinically significant disease. A systematic search was conducted on PubMed for publications from July 2008 to July 2018 in accordance with PRISMA guidelines to report biomarkers with respect to their application in PCa diagnosis, progression, aggressiveness, recurrence, and treatment response. The vast majority of studies report biomarkers with the ability to distinguish malignant from benign prostate tissue with a few studies investigating biomarkers associated with disease progression, treatment response or tumour recurrence. In general, these studies report high dimensional datasets and the number of analysed metabolites often significantly exceeded the number of available samples. Hence, observed multivariate differences between case and control samples in the datasets might potentially also be associated with pre-analytical, technical, statistical and confounding factors. Giving the technical and methodological hurdles, there are nevertheless a number of metabolites and pathways repeatedly reported across various technical approaches, cohorts and sample types that appear to play a predominant role in PCa tumour biology, progression and recurrence.
PubMed: 30791464
DOI: 10.3390/diagnostics9010021