Summary of study ST001422

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000730. The data can be accessed directly via it's Project DOI: 10.21228/M89X1C This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001422
Study TitleAspirin Metabolomics in Colorectal Cancer Chemoprevention - blood (part-II)
Study SummarySubstantial evidence supports the effectiveness of aspirin for cancer chemoprevention in addition to its well established role in cardiovascular protection. In recent meta-analyses of randomized controlled trials in human, daily aspirin use reduced incidence, metastasis and mortality from several common types of cancer, especially colorectal cancer. The mechanism(s) by which aspirin exerts an anticancer benefit is uncertain; numerous effects have been described involving both cyclooxygenase-dependent and -independent pathways. The goal of this research is to elucidate the key metabolic changes that are responsible for the anticancer effects of aspirin in humans using untargeted metabolomics analysis. Metabolomics, or global metabolite profiling, is an emerging discipline that has the potential to transform the study of pharmaceutical agents. Our innovative approach will use high-resolution mass spectroscopy to detect thousands of metabolites in blood plasma that were collected from participants in the Aspirin/Folate Polyp Prevention Study, a randomized, double-blind, placebo-controlled trial of aspirin for the prevention of colorectal adenomas. Participants in the trial were assigned with equal probability to three aspirin treatment arms (placebo, 81mg, or 325mg daily). Over the three-year period, 81mg/day of aspirin reduced the risk of adenomas, whereas the 325 mg/day dose had less effect. The aims of the current proposal are to identify metabolomic signatures, including specific metabolites and metabolic pathways, that are associated with aspirin treatment in blood of participants after three years of randomized aspirin treatment; and then to assess the associations of these metabolic signatures with adenoma risk and whether they mediate the reductions in risk due to 81 mg/day aspirin treatment. We will prioritize metabolites for study by evaluating metabolite levels in patients from the placebo and treatment arms while controlling the false discovery rate, use correlation analysis to enhance identification of relevant metabolic modules associated with these prioritized metabolites, and apply pathway mapping with post-hoc application of ion dissociation spectroscopy to representative metabolites to confirm pathway identification. Because aspirin is a multifunctional drug that is thought to modify numerous pathways with potential roles in carcinogenesis, a global discovery-based metabolomics approach is the best way to identify its key activities. The public health significance of this work is substantial because understanding the mechanism of aspirin's anticancer effects is key to optimizing its use and to the development of novel drugs targeting the metabolic pathways identified.
Institute
Emory University
DepartmentSchool of Medicine
LaboratoryClincal Biomarkers Laboratory
Last NameUppal
First NameKaran
Address615 Michael St, Suite 225
Emailkuppal2@emory.edu
Phone(404) 727 5027
Submit Date2019-10-31
Total Subjects600
Study CommentsAspirin Metabolomics Priority 1
Raw Data AvailableYes
Raw Data File Type(s).raw
Analysis Type DetailLC-MS
Release Date2020-07-20
Release Version1
Karan Uppal Karan Uppal
https://dx.doi.org/10.21228/M89X1C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN002378 AN002379
Analysis type MS MS
Chromatography type HILIC Reversed phase
Chromatography system Dionex UltiMate 3000 Dionex UltiMate 3000
Column Thermo Fisher Accucore HILIC 50x2.1mm 2.6u with Thermo accucore HILIC guard cartridge Thermo Fisher Accucore C18 50x2.1mm 2.6u with Thermo accucore
MS Type ESI ESI
MS instrument type Orbitrap Orbitrap
MS instrument name Thermo Q Exactive HF hybrid Orbitrap Thermo Q Exactive HF hybrid Orbitrap
Ion Mode POSITIVE POSITIVE
Units peak area peak area

Chromatography:

Chromatography ID:CH001745
Chromatography Summary:The HILIC column is operated parallel to reverse phase column for simultaneous analytical separation and column flushing through the use of a dual head HPLC pump equipped with 10-port and 6-port switching valves. During operation of HILIC separation method, the MS is operated in positive ion mode and 10 microliters of sample is injected onto the HILIC column while the reverse phase column is flushing with wash solution. Flow rate is maintained at 0.35 mL/min until 2 min, increased to 0.4 mL/min at 6 min and held for 4 min. Solvent A is 100% LC-MS grade water, solvent B is 100% LC-MS grade acetonitrile and solvent C is 2% formic acid (v/v) in LC-MS grade water. Initial mobile phase conditions are 25% A, 70% B, 5% C hold for 2 min, with linear gradient to 75% A, 20% B, 5% C at 6 min, hold for 4 min, resulting in a total analytical run time of 10 min. During the flushing phase (reverse phase analytical separation), the HILIC column is equilibrated with a wash solution of 25% A, 70% B, 5% C.
Methods ID:2% formic acid in LC-MS grade water
Methods Filename:20160120_posHILIC120kres10min_ESI_c18poswash_acrore.meth
Chromatography Comments:Triplicate injections for each chromatography mode
Instrument Name:Dionex UltiMate 3000
Column Name:Thermo Fisher Accucore HILIC 50x2.1mm 2.6u with Thermo accucore HILIC guard cartridge
Column Temperature:60C
Sample Injection:10 uL
Solvent A:LC-MS grade water
Solvent B:LC-MS grade acetonitrile
Analytical Time:10 min
Sample Loop Size:15 uL
Sample Syringe Size:100 uL
Chromatography Type:HILIC
  
Chromatography ID:CH001746
Chromatography Summary:The C18 column is operated parallel to the HILIC column for simultaneous analytical separation and column flushing through the use of a dual head HPLC pump equipped with 10-port and 6- port switching valves. During operation of the C18 method, the MS is operated in negative ion mode and 10 uL of sample is injected onto the C18 column while the HILIC column is flushing with wash solution. Flow rate is maintained at 0.35 mL/min until 2 min, increased to 0.4 mL/min at 6 min and held for 4 min. Solvent A is 100% LC-MS grade water, solvent B is 100% LC-MS grade acetonitrile and solvent C is 2% formic acid (v/v) in LC-MS grade water. Initial mobile phase conditions are 80% A, 15% B, 5% C hold for 0.5 min, with linear gradient to 0% A, 95% B, 5% C at 2 min, hold for 4min, resulting in a total analytical run time of 10 min. During the flushing phase (HILIC analytical separation), the C18 column is equilibrated with a wash solution of 0% A, 95% B, 5% C until 7.5 min, followed by an equilibration solution of 80% A, 15% B, 5% C for 2.5 min.
Methods Filename:20160120_posC18120kres10mim_ESI_hilicposwash_acore.meth
Instrument Name:Dionex UltiMate 3000
Column Name:Thermo Fisher Accucore C18 50x2.1mm 2.6u with Thermo accucore
Column Temperature:60C
Flow Rate:0.35 mL/min for 2 min; linear increase to 0.4 mL/min at 6 min held for 4 min
Sample Injection:10 uL
Solvent A:LC-MS grade water
Solvent B:LC-MS grade acetonitrile
Analytical Time:10 min
Sample Loop Size:15 uL
Sample Syringe Size:100 uL
Chromatography Type:Reversed phase
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