Summary of Study ST001091
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.
| Study ID | ST001091 |
| Study Title | Aspirin Metabolomics in Colorectal Cancer Chemoprevention (part 1 - Colon) |
| Study Type | Untargeted high-resolution mass spectrometry profiling |
| Study Summary | Substantial 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 humans, 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 and normal colon mucosa biopsies that were collected from participants in the Aspirin/Folate Polyp Prevention Study, a randomized, double-blind, placebo-controlled trial of aspirin and/or folic acid supplementation for the prevention of colorectal adenomas. Participants in the trial were assigned with equal probability to three aspirin treatment arms (placebo, 81 mg, or 325 mg daily). Over the three-year treatment period, 81 mg/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 and normal colon mucosal tissue 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 |
| Department | School of Medicine |
| Laboratory | Clincal Biomarkers Laboratory |
| Last Name | Uppal |
| First Name | Karan |
| Address | 615 Michael Street, Atlanta, GA, 30322, USA |
| kuppal2@emory.edu | |
| Phone | (404) 727 5027 |
| Submit Date | 2018-09-05 |
| Num Groups | 3 |
| Total Subjects | 325 |
| Num Males | 214 |
| Num Females | 111 |
| Study Comments | Both pooled colon tissue samples and Clinical Biomarker Laboratory pooled plasma samples were used |
| Analysis Type Detail | LC-MS |
| Release Date | 2019-09-23 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN001776 | AN001777 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 | Thermo Dionex Ultimate 3000 |
| Column | Waters XBridge Amide (50 x 2.1mm,2.5um) | Thermo Higgins C18 (50 x 2.1mm,3um) |
| MS Type | ESI | ESI |
| MS instrument type | Orbitrap | Orbitrap |
| MS instrument name | Thermo Fusion Tribrid Orbitrap | Thermo Fusion Tribrid Orbitrap |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Peak area | Peak area |
Chromatography:
| Chromatography ID: | CH001255 |
| 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 1.5 min, increased to 0.4 mL/min at 4 min and held for 1 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 22.5% A, 75% B, 2.5% C hold for 1.5 min, with linear gradient to 77.5% A," "20% B, 2.5% C at 4 min, hold for 1 min, resulting in a total analytical run time" "of 5 min. During the flushing phase (reverse phase analytical separation), the" "HILIC column is equilibrated with a wash solution of 77.5% A, 20% B, 2.5% C." |
| Methods ID: | 2% formic acid in LC-MS grade water |
| Methods Filename: | 20160920_posHILIC120kres5min_ESI_c18negwash.meth |
| Chromatography Comments: | Triplicate injections for each chromatography mode |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Waters XBridge Amide (50 x 2.1mm,2.5um) |
| Column Temperature: | 60C |
| Flow Gradient: | A= water, B= acetontrile, C= 2% formic acid in water; 22.5% A, 75% B, 2.5% C hold for 1.5 min, linear gradient to 77.5% A, 20% B, 2.5% C at 4 min, hold for 1 min |
| Flow Rate: | 0.35 mL/min for 1.5 min; linear increase to 0.4 mL/min at 4 min, hold for 1 min |
| Sample Injection: | 10 uL |
| Solvent A: | 100% water |
| Solvent B: | 100% acetonitrile |
| Analytical Time: | 5 min |
| Sample Loop Size: | 15 uL |
| Sample Syringe Size: | 100 uL |
| Chromatography Type: | HILIC |
| Chromatography ID: | CH001256 |
| 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 μL of sample is" injected onto the C18 column while the HILIC column is flushing with wash "solution. Flow rate is maintained at 0.4 mL/min until 1.5 min, increased to 0.5" "mL/min at 2 min and held for 3 min. Solvent A is 100% LC-MS grade water, solvent" B is 100% LC-MS grade acetonitrile and solvent C is 10mM ammonium acetate in "LC-MS grade water. Initial mobile phase conditions are 60% A, 35% B, 5% C hold" "for 0.5 min, with linear gradient to 0% A, 95% B, 5% C at 1.5 min, hold for 3.5" "min, resulting in a total analytical run time of 5 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 2.5 min, followed by an equilibration" "solution of 60% A, 35% B, 5% C for 2.5 min." |
| Methods ID: | 10mM ammonium acetate in LC-MS grade water |
| Methods Filename: | 20160920_negC18120kres5min_ESI_HILICposwash.meth |
| Instrument Name: | Thermo Dionex Ultimate 3000 |
| Column Name: | Thermo Higgins C18 (50 x 2.1mm,3um) |
| Column Temperature: | 60C |
| Flow Rate: | 0.4 mL/min for 1.5 min; linear increase to 0.5 mL/min at 2 min held for 3 min |
| Sample Injection: | 10 uL |
| Solvent A: | 100% water |
| Solvent B: | 100% acetonitrile |
| Analytical Time: | 5 min |
| Sample Loop Size: | 15 uL |
| Sample Syringe Size: | 100 uL |
| Chromatography Type: | Reversed phase |
