Multilevel omics for the discovery of biomarkers and therapeutic targets for stroke

Montaner, Joan; Ramiro, Laura; Simats, Alba; Tiedt, Steffen; Makris, Konstantinos; Jickling, Glen C.; Debette, Stéphanie; Sanchez, Jean‐Charles; Bustamante, Alejandro

doi:10.1038/s41582-020-0350-6

Cited by 214 publications

(152 citation statements)

References 171 publications

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“…Compared with other omics, data generated by proteomics and metabolomics are more directly related to the pathological symptoms and clinical parameters observed by patients (Rinschen and Saez-Rodriguez, 2020). Proteomics remains the most commonly used tool for discovering new biomarkers (Montaner et al, 2020). At present, the combination of multiomics has become a hot topic in the study of disease mechanism.…”

Section: Resultsmentioning

confidence: 99%

Exploration the Mechanism of Doxorubicin-Induced Heart Failure in Rats by Integration of Proteomics and Metabolomics Data

et al. 2020

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Heart failure is a common systemic disease with high morbidity and mortality worldwide. Doxorubicin (DOX) is a commonly used anthracycline broad-spectrum antitumor antibiotic with strong antitumor effect and definite curative effect. However, cardiotoxicity is the adverse reaction of drug dose cumulative toxicity, but the mechanism is still unclear. In this study, proteomics and metabonomics techniques were used to analyze the tissue and plasma of DOX-induced heart failure (HF) in rats and to clarify the molecular mechanism of the harmful effects of DOX on cardiac metabolism and function in rats from a new point of view. The results showed that a total of 278 proteins with significant changes were identified by quantitative proteomic analysis, of which 118 proteins were significantly upregulated and 160 proteins were significantly downregulated in myocardial tissue. In the metabonomic analysis, 21 biomarkers such as L-octanoylcarnitine, alpha-ketoglutarate, glutamine, creatine, and sphingosine were detected. Correlation analysis showed that DOX-induced HF mainly affected phenylalanine, tyrosine, and tryptophan biosynthesis, D-glutamine and D-glutamate metabolism, phenylalanine metabolism, biosynthesis of unsaturated fatty acids, and other metabolic pathways, suggesting abnormal amino acid metabolism, fatty acid metabolism, and glycerol phospholipid metabolism. It is worth noting that we have found the key upstream target of DOX-induced HF, PTP1B, which inhibits the expression of HIF-1α by inhibiting the phosphorylation of IRS, leading to disorders of fatty acid metabolism and glycolysis, which together with the decrease of Nrf2, SOD, Cytc, and AK4 proteins lead to oxidative stress. Therefore, we think that PTP1B may play an important role in the development of heart failure induced by doxorubicin and can be used as a potential target for the treatment of heart failure.

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Section: Resultsmentioning

confidence: 99%

Exploration the Mechanism of Doxorubicin-Induced Heart Failure in Rats by Integration of Proteomics and Metabolomics Data

et al. 2020

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“…For high-throughput EV biomarker discovery, flow cytometry is limited but may be implemented in downstream diagnostic tests when the pathology-specific markers have already been determined (described in further detail below). More in-depth and explorative analysis of EV protein composition using proteomic techniques such as liquid chromatography fractionation in conjunction with tandem mass spectrometry (LC/MS/MS) have been reported in several studies, including studies that investigated the proteomic profile of circulating stroke EVs [ 55 , 56 , 57 ]. To date, only one study by Couch et al investigated the proteomic profile of EVs released in the acute phase after ischemic stroke (<24 h) [ 56 ].…”

Section: Ev Isolation and Characterizationmentioning

confidence: 99%

Extracellular Vesicles in Acute Stroke Diagnostics

et al. 2020

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There is a large unmet need for fast and reliable diagnostics in several diseases. One such disease is stroke, where the efficacy of modern reperfusion therapies is highly time-dependent. Diagnosis of stroke and treatment initiation should be performed as soon as possible, and preferably before arrival at the stroke center. In recent years, several potential blood biomarkers for stroke have been evaluated, but without success. In this review, we will go into detail on the possibility of utilizing extracellular vesicles (EVs) released into the blood as novel biomarkers for stroke diagnostics. EVs are known to reflect the immediate state of the secreting cells and to be able to cross the blood–brain barrier, thus making them attractive as diagnostic biomarkers of brain diseases. Indeed, several studies have reported EV markers that enable differentiation between stroke patients and controls and, to a lesser extent, the ability to correctly classify the different stroke types. Most of the studies rely on the use of sophisticated and time-consuming methods to quantify specific subpopulations of the nanosized EVs. As these methods cannot be easily implemented in a rapid point of care (POC) test, technical developments followed by prospective clinical studies are needed.

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“…A biomarker should be specific (reflect the extent of brain damage), sensitive (easily detected), and selective (reflect therapeutic efficacy) [ 56 , 57 ]. Stroke is associated with a variety of pathophysiological changes, which lead to the triggering of different biochemical processes and related biomarkers [ 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. Over the past decades, B-type natriuretic peptide (BNP) and its derivative N-terminal pro-BNP (NT-proBNP) have been increasingly investigated and highlighted as significant cardiovascular biomarkers, especially for heart failure (HF) and recently also for stroke [ 71 , 72 ].…”

Section: Introductionmentioning

confidence: 99%

B-Type Natriuretic Peptide as a Significant Brain Biomarker for Stroke Triaging Using a Bedside Point-of-Care Monitoring Biosensor

et al. 2020

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Stroke is a widespread condition that causes 7 million deaths globally. Survivors suffer from a range of disabilities that affect their everyday life. It is a complex condition and there is a need to monitor the different signals that are associated with it. Stroke patients need to be rapidly diagnosed in the emergency department in order to allow the admission of the time-limited treatment of tissue plasminogen activator (tPA). Stroke diagnostics show the use of sophisticated technologies; however, they still contain limitations. The hidden information and technological advancements behind the utilization of biomarkers for stroke triaging are significant. Stroke biomarkers can revolutionize the way stroke patients are diagnosed, monitored, and how they recover. Different biomarkers indicate different cascades and exhibit unique expression patterns which are connected to certain pathologies in the human body. Over the past decades, B-type natriuretic peptide (BNP) and its derivative N-terminal fragment (NT-proBNP) have been increasingly investigated and highlighted as significant cardiovascular biomarkers. This work reviews the recent studies that have reported on the usefulness of BNP and NT-proBNP for stroke triaging. Their classification association is also presented, with increased mortality in stroke, correlation with cardioembolic stroke, and an indication of a second stroke recurrence. Moreover, recent scientific efforts conducted for the technological advancement of a bedside point-of-care (POC) device for BNP and NT-proBNP measurements are discussed. The conclusions presented in this review may hopefully assist in the major efforts that are currently being conducted in order to improve the care of stroke patients.

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Multilevel omics for the discovery of biomarkers and therapeutic targets for stroke

Cited by 214 publications

References 171 publications

Exploration the Mechanism of Doxorubicin-Induced Heart Failure in Rats by Integration of Proteomics and Metabolomics Data

Exploration the Mechanism of Doxorubicin-Induced Heart Failure in Rats by Integration of Proteomics and Metabolomics Data

Extracellular Vesicles in Acute Stroke Diagnostics

B-Type Natriuretic Peptide as a Significant Brain Biomarker for Stroke Triaging Using a Bedside Point-of-Care Monitoring Biosensor

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