LC-hrms metabolomics profiling in breast cancer: Searching for biomarkers in human plasma samples.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23053-e23053
Author(s):  
Pedro Sánchez Rovira ◽  
Ana Laura Ortega Granados ◽  
Mónica Fernández Navarro ◽  
María Ruiz Sanjuan ◽  
Capilla de la Torre Cabrera ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
New Technologies ◽  
Biomarker Discovery ◽  
Environmental Changes ◽  
Plasma Samples ◽  
Diagnostic Biomarkers ◽  
Wide Range ◽  
Significant Difference

e23053 Background: Breast cancer (BC) is most common cancer in women and development of new technologies for understanding molecular changes involved in BC progression is essential. Metabolic changes precede phenotypic changes, due to cellular regulation affects use of small-molecule substrates for cell division, growth or environmental changes, such as hypoxia. Metabolomics (profiling of metabolites in biofluid, cell and tissue) is routinely applied as a tool for biomarker discovery. Liquid chromatography−mass spectrometry(LC−MS)is the dominating platform. Methods: With the aim to find metabolomic profiles for diagnostic and prognostic of newly diagnosticated breast cancer (BC) we have investigated plasma samples in neoadjuvant setting (134 BC patients with median age of 51 years, stages T1-4,N1-2,M0 and 135 healthy controls) using high resolution mass spectrometry couple to liquid chromatography in reverse phase and HILIC modes which provided resolved chromatography of highly polar as well as hydrophobic analytes, enabling the analysis of a wide range of chemicals, necessary for untargeted metabolomics. Chromatograms were processed with software (Markerview) to generate a table listing retention times with associated ion masses and intensities. To identify potential biomarkers, we used in combination 2 independent variable selection techniques: principal component analysis and Student t-test. Results: We observed a significant difference in metabolic profile between the 2 groups. 15 molecular features [oleamide, KDNalpha2-3Galbeta1-4Glcbeta-Cer(d18:1/22:0)] were found significantly down/up regulated in BC patients compared with healthy subjects, and they were selected as diagnostic biomarkers. Additionally, ROC curve analysis was used to assess their clinical usefulness, obtaining an AUC of 0.963 (95% CI 0.919-0.989) when using a multivariate model of 3 features. As an outcome, we showed that selected biomarkers are useful as diagnostic biomarkers. Conclusions: The present study demonstrates potential of metabolomics in identifying novel biomarkers for BC. Further studies may reveal the potential of metabolites as diagnostics biomarkers for BC and their role in pathogenesis.

scholarly journals Discovery and Verification of Gelsolin as a Potential Biomarker of Colorectal Adenocarcinoma in a Chinese Population: Examining Differential Protein Expression using an Itraq Labelling-Based Proteomics Approach

2012 ◽  
Vol 26 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Nai-Jun Fan ◽  
Chun-Fang Gao ◽  
Chang-Song Wang ◽  
Jing-Jing Lv ◽  
Guang Zhao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Protein Identification ◽  
Colorectal Adenocarcinoma ◽  
Biomarker Discovery ◽  
Differentially Expressed ◽  
Screening Tests ◽  
Differentially Expressed Proteins ◽  
Potential Biomarker ◽  
Wide Range

Despite the wide range of available colorectal cancer (CRC) screening tests, less than 50% of cases are detected at early stages. However, the identification of differentially expressed proteins or novel protein biomarkers in CRC may have some utility and, ultimately, improve patient care and survival. Proteomics combined with mass spectroscopy and liquid chromatography are emerging as powerful tools that have led to the discovery of potential markers in cancer biomarker discovery in several types of cancers. This article describes a novel technology that uses isotopic reagents to tag selected proteins that show a consistent pattern of differential expression in CRC.OBJECTIVE: To identify and validate potential biomarkers of colorectal adenocarcinoma using a proteomic approach.METHODS: Multidimensional liquid chromatography/mass spectrometry was used to analyze biological samples labelled with isobaric mass tags for relative and absolute quantitation to identify differentially expressed proteins in human colorectal adenocarcinoma and paired normal mucosa for the discovery of cancerous biomarkers. Cancerous and noncancerous samples were compared using online and offline separation. Protein identification was performed using mass spectrometry. The downregulation of gelsolin protein in colorectal adenocarcinoma samples was confirmed by Western blot analysis and validated using immunohistochemistry.RESULTS: A total of 802 nonredundant proteins were identified in colorectal adenocarcinoma samples, 82 of which fell outside the expression range of 0.8 to 1.2, and were considered to be potential cancer-specific proteins. Immunohistochemistry revealed a complete absence of gelsolin expression in 86.89% of samples and a reduction of expression in 13.11% of samples, yielding a sensitivity of 86.89% and a specificity of 100% for distinguishing colorectal adenocarcinoma from normal tissue.CONCLUSIONS: These findings suggest that decreased expression of gelsolin is a potential biomarker of colorectal adenocarcinoma.

scholarly journals Human Plasma Metabolomics for Biomarker Discovery: Targeting the Molecular Subtypes in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 147
Author(s):  
Leticia Díaz-Beltrán ◽  
Carmen González-Olmedo ◽  
Natalia Luque-Caro ◽  
Caridad Díaz ◽  
Ariadna Martín-Blázquez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Biomarker Discovery ◽  
Molecular Subtypes ◽  
Breast Cancer Subtype ◽  
P Value ◽  
Plasma Samples ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Molecular Phenotypes

Purpose: The aim of this study is to identify differential metabolomic signatures in plasma samples of distinct subtypes of breast cancer patients that could be used in clinical practice as diagnostic biomarkers for these molecular phenotypes and to provide a more individualized and accurate therapeutic procedure. Methods: Untargeted LC-HRMS metabolomics approach in positive and negative electrospray ionization mode was used to analyze plasma samples from LA, LB, HER2+ and TN breast cancer patients and healthy controls in order to determine specific metabolomic profiles through univariate and multivariate statistical data analysis. Results: We tentatively identified altered metabolites displaying concentration variations among the four breast cancer molecular subtypes. We found a biomarker panel of 5 candidates in LA, 7 in LB, 5 in HER2 and 3 in TN that were able to discriminate each breast cancer subtype with a false discovery range corrected p-value < 0.05 and a fold-change cutoff value > 1.3. The model clinical value was evaluated with the AUROC, providing diagnostic capacities above 0.85. Conclusion: Our study identifies metabolic profiling differences in molecular phenotypes of breast cancer. This may represent a key step towards therapy improvement in personalized medicine and prioritization of tailored therapeutic intervention strategies.

Developments in mycotoxin analysis: an update for 2012-2013

2014 ◽  
Vol 7 (1) ◽  
pp. 3-33 ◽  
Author(s):  
F. Berthiller ◽  
P.A. Burdaspal ◽  
C. Crews ◽  
M.H. Iha ◽  
R. Krska ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Sample Preparation ◽  
Ergot Alkaloids ◽  
Tandem Mass ◽  
Wide Range ◽  
Rapid Spread ◽  
Food And Feed ◽  
Mycotoxin Analysis ◽  
The Individual

This review highlights developments in mycotoxin analysis and sampling over a period between mid-2012 and mid-2013. It covers the major mycotoxins: aflatoxins, Alternaria toxins, ergot alkaloids, fumonisins, ochratoxins, patulin, trichothecenes and zearalenone. A wide range of analytical methods for mycotoxin determination in food and feed were developed last year, in particular immunochemical methods and liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)-based methods. After a section on sampling and sample preparation, due to the rapid spread and developments in the field of LC-MS/MS multimycotoxin methods, a separate section has been devoted to this area of research. It is followed by a section on mycotoxins in botanicals and spices, before continuing with the format of previous reviews in this series with dedicated sections on method developments for the individual mycotoxins.

scholarly journals A RAPID, SENSITIVE AND VALIDATED ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY AND TANDEM MASS SPECTROMETRY METHOD FOR DETERMINATION OF RIFAMPICIN IN RAT PLASMA: APPLICATION TO PHARMACOKINETIC STUDY

2017 ◽  
Vol 9 (2) ◽  
pp. 222
Author(s):  
Aslam Burhan ◽  
Bhavin Vyas
Keyword(s):  
Mass Spectrometry ◽  
Quality Control ◽  
Liquid Chromatography ◽  
Drug Interaction ◽  
Tandem Mass Spectrometry ◽  
Ultra Performance Liquid Chromatography ◽  
Rat Plasma ◽  
Tandem Mass ◽  
Plasma Samples ◽  
Interaction Studies

<p><strong>Objective: </strong>To develop and validate simple, sensitive and selective ultra-performance liquid chromatography and tandem mass spectrometry (UPLC-MS/MS) method for quantification of rifampicin (RIF) in rat plasma and its application to pharmacokinetics study.</p><p><strong>Methods: </strong>Precipitation method was used for the extraction of plasma samples, an aliquot of 25 µl plasma samples was extracted using acetonitrile precipitation technique. Chromatographic separation was performed usingWaters Acquity<sup>TM</sup>UPLC columns, BEH C18 (50 mm× 2.1 mm, 1.7 µm) by a gradient mixture of acetonitrile and water (both containing 0.1 % formic acid) as a mobile phase at the flow rate of 0.7 ml/min.The analyte was protonated in the positive ESI (electrospray ionization interface) and detected in MRM (multiple reactions monitoring) modes using the transition m/z 308.60-455.30.</p><p><strong>Results: </strong>The method had a short chromatography run time of 1.8 min with improved sensitivity over existing methods. Calibration curves been linear over the wide range of 1.97-5047.00 ng/ml. The between and within-batch precision and accuracy of the method was determined by using 4 quality control samples; the highest %CV observed was10.11. The mean recovery values are 74.26, 82.77 and 101.73 at low, medium and high-quality control levels; respectively.</p><p><strong>Conclusion: </strong>It was concluded that the developed and validated UPLC-MS/MS method was sensitive,specific, precise, linear, and rapid. Therefore, the method can be used for quantification of RIFin rat plasma with various advantages over the reported methods. RIF is widely recommended by US-FDAguidance for industry on drug interaction studies and the developed method can be used to explore drug interaction studies in drug discovery and development.</p>

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