Comprehensive metabolomic profiling of osteosarcoma based on UHPLC-HRMS

Abstract Introduction Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. An increasing number of studies have demonstrated that tumor proliferation and metastasis are closely related to complex metabolic reprogramming. However, there are limited data to provide a comprehensive metabolic picture of osteosarcoma. Objectives Our study aims to identify aberrant metabolic pathways and seek potential adjuvant biomarkers for osteosarcoma. Methods Serum samples were collected from 65 osteosarcoma patients and 30 healthy controls. Nontargeted metabolomic profiling was performed by liquid chromatography-mass spectrometry (LC-MS) based on univariate and multivariate statistical analyses. Results The OPLS-DA model analysis identified clear separations among groups. We identified a set of differential metabolites such as higher serum levels of adenosine-5-monophosphate, inosine-5-monophosphate and guanosine monophosphate in primary OS patients compared to healthy controls, and higher serum levels of 5-aminopentanamide, 13(S)-HpOTrE (FA 18:3 + 2O) and methionine sulfoxide in lung metastatic OS patients compared to primary OS patients, revealing aberrant metabolic features during the proliferation and metastasis of osteosarcoma. We found a group of metabolites especially lactic acid and glutamic acid, with AUC values of 0.97 and 0.98, which could serve as potential adjuvant diagnostic biomarkers for primary osteosarcoma, and a panel of 2 metabolites, 5-aminopentanamide and 13(S)-HpOTrE (FA 18:3 + 2O), with an AUC value of 0.92, that had good monitoring ability for lung metastases. Conclusions Our study provides new insight into the aberrant metabolic features of osteosarcoma. The potential biomarkers identified here may have translational significance.

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Antibodies to Der p 1 and Der p 2 in allergic patients

Allergologia et Immunopathologia ◽

10.15586/aei.v49i2.59 ◽

2021 ◽

Vol 49 (2) ◽

pp. 46-52

Author(s):

Renata Harumi Cruz ◽

Leandro Hideki Ynoue ◽

Carolina Sanchez Aranda ◽

Dirceu Solé ◽

Antonio Condino Neto

Keyword(s):

Serum Levels ◽

Specific Ige ◽

Protective Mechanism ◽

Healthy Controls ◽

Healthy Individuals ◽

Serum Samples ◽

Th2 Response ◽

Iga Antibodies ◽

Der P 1 ◽

Der P 2

Introduction and objectives: Atopic individuals are characterized by increased IgE production and Th2 response if exposed to certain antigens. It is known that the mother transfers antimite antibodies to the fetus and newborn, IgG thru the placenta, and IgA thru breastfeeding, but it is not clear whether there is a protective mechanism mediated by them concerning the development of future allergies. This study aimed to compare the levels of IgA, IgG, and IgE antibodies specific to Der p 1 and Der p 2 between atopic and healthy individuals.Methods: Serum samples of 98 patients and 44 healthy controls were subjected to quantification for specific IgE, IgG, and IgA antibodies against Der p 1 and Der p 2 by ImmunoCap® and ELISA, and subjected to statistical analysis as indicated.Results: Atopic patients had higher serum levels of IgE, IgG, and IgA specific to Der p 1 and Der p 2. The correlation was more robust between IgE and IgG antibodies.Conclusions: Allergic patients produce higher levels of antibodies against Der p 1 and Der p 2 compared with healthy individuals. The mechanisms involved still require detailed studies.

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0054 Metabolite Profiles of Obstructive Sleep Apnea Distinguishes Cases from Controls and Improve With CPAP

SLEEP ◽

10.1093/sleep/zsaa056.052 ◽

2020 ◽

Vol 43 (Supplement_1) ◽

pp. A21-A22

Author(s):

A Sengupta ◽

D C Lim ◽

B T Keenan ◽

L Keele ◽

A Pack ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Methionine Sulfoxide ◽

Ultra Performance Liquid Chromatography ◽

Healthy Controls ◽

Serum Samples ◽

Metabolomics Data ◽

Cpap Treatment ◽

Clinical Biomarkers ◽

Obstructive Sleep

Abstract Introduction Obstructive sleep apnea (OSA) is a common sleep breathing disorder with significant public health consequences. Despite this, no clinically available objective molecular biomarkers to diagnose, risk stratify and quantify treatment efficiency exist. To this end, high-throughput metabolomics data could serve as a valuable quantitative tool. Methods We designed a pilot study to investigate the metabolomic effects of OSA and CPAP treatment. Blood serum samples were collected from OSA patients and healthy controls matched with respect to age (±5 years), BMI (±2.5 kg/m2) and gender (N = 20/group). Samples from OSA patients were obtained before and after continuous positive airway pressure (CPAP) treatment. Polar metabolites were analyzed using a targeted ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) metabolomics technique. Results Supervised multivariate analysis using serum metabolic values of OSA patients and healthy controls showed a significantly different overall metabolic profile between the two groups (orthogonal partial least squares discriminant analysis [OPLS-DA] Q2=0.25, p=0.04). Acetylornithine, choline, cytidine, dodecenoylcarnitine, methionine sulfoxide and 3-indoxylsulfate were among the most perturbed metabolites. Major metabolic pathways altered in the OSA patients were methionine and phospholipid metabolism, as well as gut microbial co-metabolism. Lysophosphatidylcholine (16:0), a phospholipid metabolite, demonstrated significant linear association with improved oxygen saturation nadir post CPAP treatment (R2 = 0.57), suggesting the metabolic features may be used as prognostic clinical biomarkers. Conclusion These results suggest that OSA significantly impacts blood metabolites, which could potentially be used to establish OSA biomarkers. Moreover, specific metabolic features are associated with post CPAP improvement, such as phospholipids, suggesting a functional association of these metabolites that may help us understand the heterogeneity of OSA. Overall, these results demonstrate the potential of metabolic profiling to develop quantitative molecular markers of OSA. Further studies are underway to validate these findings and investigate the utility of metabolic profiles to objectively measure CPAP efficacy. Support The work was supported by the program project grant P01 HL094307.

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Extracellular Vesicle-Based Detection of Pancreatic Cancer

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.697939 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yesim Verel-Yilmaz ◽

Juan Pablo Fernández ◽

Agnes Schäfer ◽

Sheila Nevermann ◽

Lena Cook ◽

...

Keyword(s):

High Sensitivity ◽

Roc Curves ◽

Serum Levels ◽

Extracellular Vesicle ◽

Ductal Adenocarcinoma ◽

Rank Test ◽

Healthy Controls ◽

Precursor Lesions ◽

Healthy Individuals ◽

Serum Samples

Due to a grim prognosis, there is an urgent need to detect pancreatic ductal adenocarcinoma (PDAC) prior to metastasis. However, reliable diagnostic imaging methods or biomarkers for PDAC or its precursor lesions are still scarce. ADAM8, a metalloprotease-disintegrin, is highly expressed in PDAC tissue and negatively correlates with patient survival. The aim of our study was to determine the ability of ADAM8-positive extracellular vesicles (EVs) and cargo microRNAs (miRNAs) to discriminate precursor lesions or PDAC from healthy controls. In order to investigate enrichment of ADAM8 on EVs, these were isolated from serum of patients with PDAC (n = 52), precursor lesions (n = 7) and healthy individuals (n = 20). Nanoparticle Tracking Analysis and electron microscopy indicated successful preparation of EVs that were analyzed for ADAM8 by FACS. Additionally, EV cargo analyses of miRNAs from the same serum samples revealed the presence of miR-720 and miR-451 by qPCR and was validated in 20 additional PDAC samples. Statistical analyses included Wilcoxon rank test and ROC curves. FACS analysis detected significant enrichment of ADAM8 in EVs from patients with PDAC or precursor lesions compared to healthy individuals (p = 0.0005). ADAM8-dependent co-variates, miR-451 and miR-720 were also diagnostic, as patients with PDAC had significantly higher serum levels of miR-451 and lower serum levels of miR-720 than healthy controls and reached high sensitivity and specificity (AUC = 0.93 and 1.00, respectively) to discriminate PDAC from healthy control. Thus, detection of ADAM8-positive EVs and related cargo miR-720 and miR-451 may constitute a specific biomarker set for screening individuals at risk for PDAC.

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Metabolomic approach to Alzheimer’s disease diagnosis based on mass spectrometry

Chemical Papers ◽

10.2478/s11696-012-0184-9 ◽

2012 ◽

Vol 66 (9) ◽

Cited By ~ 17

Author(s):

Raúl González-Domínguez ◽

Tamara García-Barrera ◽

José-Luis Gómez-Ariza

Keyword(s):

Mass Spectrometry ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Diagnosis ◽

Healthy Controls ◽

Serum Samples ◽

Statistical Tools ◽

Multivariate Statistical ◽

New Biomarkers ◽

Metabolomic Approach

AbstractAlzheimer’s disease is the most common neurodegenerative disease, but there is still no cure and early diagnosis remains very difficult. For this reason, the discovery of new biomarkers is of great importance. The application of metabolomics is emerging in this field, based on the use of mass spectrometry as a technique of analysis. In this work, blood serum samples (from Alzheimer’s disease patients and healthy controls) were analysed by mass spectrometry in order to search for potential metabolomic biomarkers. The application of multivariate statistical tools (PLS-DA) enabled us to discriminate between groups. In addition, some phosphatidylcholine compounds were identified as markers of the disease.

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Serum levels of TIMP-1 and MMP-7 as potential biomarkers in patients with metastatic colorectal cancer

The International Journal of Biological Markers ◽

10.1177/1724600819866202 ◽

2019 ◽

Vol 34 (3) ◽

pp. 292-301 ◽

Cited By ~ 1

Author(s):

Michal Vočka ◽

Daniel Langer ◽

Vladimir Fryba ◽

Jaromir Petrtyl ◽

Tomas Hanus ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Carcinoembryonic Antigen ◽

Serum Levels ◽

Healthy Controls ◽

Serum Samples ◽

Gastrointestinal Malignancies ◽

Matrix Metalloproteinase 7 ◽

Growth Promoting ◽

Potent Growth

Objective: Tissue inhibitor of metalloproteinases 1 (TIMP-1) and matrix metalloproteinase 7 (MMP-7) were reported to have potent growth promoting activity. Lack of balance between MMPs and TIMPs is an important factor in the development of gastrointestinal malignancies. Methods: We collected serum samples from 97 patients with metastatic colorectal cancer and 79 samples from healthy controls. Serum levels of TIMP-1 and MMP-7 were measured immunochemically and compared with standard tumor markers carcinoembryonic antigen and CA19-9. Results: Serum levels of TIMP-1 and MMP-7 were significantly higher in patients with colorectal cancer compared to healthy controls (both, P < 0.001). TIMP-1 and MMP-7 correlate with the presence of colon involvement (P = 0.001; P = 0.012) and the presence of liver metastases (P = 0.002; P = 0.037), and negatively correlate with pulmonary metastases (P = 0.014; P = 0.005). MMP-7 had similar sensitivity and the same specificity as carcinoembryonic antigen. TIMP-1 and MMP-7 had better sensitivity than CA19-9. TIMP-1 and MMP-7 level correlate with worse outcome (P = 0.002). Conclusion: The results indicate that TIMP-1 and MMP-7 are effective biomarkers in patients with metastatic colorectal cancer with good sensitivity. TIMP-1 and MMP-7 levels strongly correlate with the extent of liver disease and have prognostic value.

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Serum Metabolomic Profiling of Rats by Intervention of Aconitum soongaricum

Natural Product Communications ◽

10.1177/1934578x1501001238 ◽

2015 ◽

Vol 10 (12) ◽

pp. 1934578X1501001

Author(s):

Fan Zhang ◽

Jiao Liu ◽

Jun Lei ◽

Wenjing He ◽

Yun Sun

Keyword(s):

Statistical Analysis ◽

Nmr Spectroscopy ◽

Metabolic Profiles ◽

Metabolomic Analysis ◽

Serum Samples ◽

Multivariate Statistical ◽

H Nmr ◽

Metabolomic Profiling ◽

Clinical Detection ◽

Endogenous Metabolites

To understand the toxic mechanism and to find the changes in the endogenous metabolites of Aconitum soongaricum Stapf for clinical detection, a combination of 1H NMR spectroscopy and multivariate statistical analysis was applied to examine the metabolic profiles of the blood serum samples collected from the rat model. In total, thirteen biomarkers of A. soongaricum were found and identified. It turned out that A. soongaricum treatment may partially disorder the metabolism. The study has shown the potential application of NMR-based metabolomic analysis in providing further insights into the toxicity caused by A. soongaricum.

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Myristic Acid Serum Levels and Their Significance for Diagnosis of Systemic Inflammatory Response, Sepsis, and Bacteraemia

Journal of Personalized Medicine ◽

10.3390/jpm11040306 ◽

2021 ◽

Vol 11 (4) ◽

pp. 306

Author(s):

Roman Zazula ◽

Michal Moravec ◽

František Pehal ◽

Tomáš Nejtek ◽

Marek Protuš ◽

...

Keyword(s):

Inflammatory Response ◽

Myristic Acid ◽

Close Correlation ◽

Serum Levels ◽

Severe Trauma ◽

Systemic Inflammatory Response ◽

Sepsis Group ◽

Trauma Patients ◽

Healthy Controls ◽

Serum Samples

Myristic acid is identified as a metabolite with the highest diagnostic sensitivity and specificity in the metabolome of patients with bacteraemia. Its significant decrease has been observed in patients with septic shock not responding to treatment. Another study has reported a close correlation of myristic acid levels with the outcome of severe trauma patients. Myristic acid concentrations were investigated in a cohort of septic patients and patients with Systemic Inflammatory Response Syndrome (SIRS) in 5 consecutive days following diagnosis and compared to healthy controls. The study population groups—Sepsis 34, SIRS 31, and Healthy Control 120 patients were included. Serum samples were analyzed using gas chromatography and mass spectrometry. The myristic acid levels in the Sepsis Group and SIRS Group were found to be significantly higher when compared to healthy controls. The serum concentration of myristic acid in septic patients with bacteraemia was higher than in septic patients without bacteraemia. Most patients with sepsis and SIRS had the highest levels of myristic acid within 24 h after an established diagnosis. Myristic acid should be considered as a new candidate marker of severe inflammation and sepsis. A simplified analysis and sufficient body of validated data are necessary steps towards the introduction of this metabolite into routine clinical practice.

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Soluble selectins and highly fucosylated ?1-antichymotrypsin in rheumatoid arthritis patients

Journal of Medical Science ◽

10.20883/medical.e33 ◽

2015 ◽

Vol 84 (1) ◽

pp. 34-40

Author(s):

Anna Olewicz-Gawlik ◽

Izabela Korczowska-Łącka ◽

Paweł Hrycaj

Keyword(s):

Rheumatoid Arthritis ◽

Rheumatoid Factor ◽

Acute Phase Proteins ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Serum Concentrations ◽

Serum Samples ◽

Male And Female ◽

Leukocyte Extravasation

Introduction. Fucosylation of acute phase proteins and serum soluble selectin levels is increased in rheumatoid arthritis (RA) patients and can influence leukocyte extravasation. Aim. The aim of this study was to evaluate the concentration and fucosylation of ?1-antichymotrypsin (ACT) in relation to serum concentrations of soluble forms of selectins in RA patients. Material and methods. Serum samples of 70 RA patients and 30 healthy controls were examined using sandwich enzyme-linked immunosorbent assay (ELISA). Results. ACT-FR was significantly increased in RA patients when compared to healthy controls (p < 0.001) and significantly correlated with serum concentrations of rheumatoid factor (RF) and antibodies against cyclic citrullinated peptides (ACPA) (p = 0.006, p = 0.04, respectively). Moreover, we found significant correlations between the serum levels of soluble (s)P- and sE-selectin and ACT-FR (p = 0.008 and p = 0.03, respectively) only in male RA patients.Conclusions. Fucosylation of ACT differs between male and female RA patients and is related to sP- and sE-selectin levels only in men.

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Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer

Disease Markers ◽

10.1155/2021/6858809 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Chengjian Zhang ◽

Shengnan Zhou ◽

Huijing Chang ◽

Feng Zhuang ◽

Yang Shi ◽

...

Keyword(s):

Colorectal Cancer ◽

Metabolic Pathways ◽

Roc Curves ◽

Serum Levels ◽

Serum Biomarkers ◽

Healthy Controls ◽

Dodecylbenzenesulfonic Acid ◽

Metabolomic Profiling ◽

Liquid Chromatography Tandem Mass ◽

Healthy Control

Background. The screening and early detection of colorectal cancer (CRC) still remain a challenge due to the lack of reliable and effective serum biomarkers. Thus, this study is aimed at identifying serum biomarkers of CRC that could be used to distinguish CRC from healthy controls. Methods. A prospective 1 : 2 individual matching case-control study was performed which included 50 healthy control subjects and 98 CRC patients. Untargeted metabolomic profiling was conducted with liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify CRC-related metabolites and metabolic pathways. Results. In total, 178 metabolites were detected, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish CRC patients from healthy controls. Nine metabolites showed significantly differential serum levels in CRC patients under the conditions of variable importance in projection VIP > 1 , p < 0.05 using Student’s t -test, and fold change FC ≥ 1.2 or ≤0.5. The above nine metabolites were 3-hydroxybutyric acid, hexadecanedioic acid, succinic acid semialdehyde, 4-dodecylbenzenesulfonic acid, prostaglandin B2, 2-pyrocatechuic acid, xanthoxylin, 12-hydroxydodecanoic acid, and formylanthranilic acid. Four potential biomarkers were identified to diagnose CRC through ROC curves: hexadecanedioic acid, 4-dodecylbenzenesulfonic acid, 2-pyrocatechuic acid, and formylanthranilic acid. All AUC values of these four serum biomarkers were above 0.70. In addition, the exploratory analysis of metabolic pathways revealed the activated states for the vitamin B metabolic pathway and the alanine, aspartate, and glutamate metabolic pathways associated with CRC. Conclusion. The 4 identified potential metabolic biomarkers could discriminate CRC patients from healthy controls, and the 2 metabolic pathways may be activated in the CRC tissues.

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Metabolomic Characterization of Acute Ischemic Stroke Facilitates Metabolomic Biomarker Discovery

10.21203/rs.3.rs-661365/v1 ◽

2021 ◽

Author(s):

Biao Qi ◽

Yanyu Zhang ◽

Yuhao Zhang ◽

Guoqiang Fei ◽

Ling lin ◽

...

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Biomarker Discovery ◽

Multiple Reaction Monitoring ◽

Control Group ◽

Healthy Controls ◽

Serum Samples ◽

Multivariate Statistical ◽

Lysine Degradation

Abstract Acute ischemic stroke (AIS) is characterized by a sudden blockage of one of the main arteries supplying blood to the brain, leading to insufficient oxygen and nutrients for brain cells to function properly. Unfortunately, metabolic alterations in the biofluids with AIS are still not well understood. In this study, we performed high-throughput target metabolic analysis on 44 serum samples, including 22 from AIS patients and 22 from healthy controls. Multiple reaction monitoring analysis of 180 common metabolites revealed a total of 29 metabolites changed significantly (VIP>1, P <0.05). Multivariate statistical analysis unraveled a strikingly separation between AIS patients and healthy controls. Comparing AIS with Control group, the contents of argininosuccinic acid, beta-D-glucosamine, glycerophosphocholine, L-abrine, and L-pipecolic acid were down-regulated in AIS patients. 29 out of 112 detected metabolites, enriched in aminoacyl-tRNA biosynthesis, glycerophospholipid metabolism, lysine degradation, phenylalanine, tyrosine and tryptophan biosynthesis metabolic pathways. Collectively, these results will provide a sensitive, feasible diagnostic prospect for AIS patients.

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