Summary of Study ST002773
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 PR001730. The data can be accessed directly via it's Project DOI: 10.21228/M8371M 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 | ST002773 |
| Study Title | A nested case-control study of untargeted plasma metabolomics and lung cancer risk among never-smoking women in Shanghai Women’s Health Study |
| Study Summary | Background: The etiology of lung cancer among never smokers has not been fully elucidated despite 15% of cases in men and 53% in women worldwide are not smoking-related. Metabolomics provides a snapshot of dynamic biochemical activities, including those found to be driving tumor formation and progression. This study used untargeted metabolomics with network analysis to agnostically identify network modules and independent metabolites in pre-diagnostic blood samples among never-smokers to further understand the pathogenesis of lung cancer. Methods and Findings: Within the prospective Shanghai Women’s Health Study, we conducted a nested case-control study of 395 never-smoking incident lung cancer cases and 395 never-smoking controls matched on age. We performed liquid chromatography high-resolution mass spectrometry to quantify 20,348 metabolic features in plasma. We agnostically constructed 28 network modules using a weighted correlation network analysis approach and assessed associations for network modules and individual metabolites with lung cancer using conditional logistic regression models, adjusting for covariates. We accounted for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 122 metabolic features enriched in lysophosphatidylethanolamines that was associated with all lung cancer combined (p = 0.001, FDR = 0.028) and lung adenocarcinoma (p = 0.002, FDR = 0.056) and another network module of 440 metabolic features that was associated with lung adenocarcinoma (p = 0.014, FDR = 0.196). Metabolic features were enriched in pathways associated with cell growth and proliferation, including oxidative stress, bile acid biosynthesis, and metabolism of nucleic acids, carbohydrates, and amino acids, including 1-carbon compounds. Conclusions: Our prospective study suggests that untargeted plasma metabolomics in pre-diagnostic samples could provide new insights into the etiology of lung cancer in never-smokers. Replication and further characterization of these associations are warranted. |
| Institute | Emory University |
| Department | Gangarosa Department of Environmental Health |
| Laboratory | Comprehensive Laboratory for Untargeted Exposome Science |
| Last Name | Walker |
| First Name | Douglas |
| Address | 1518 Clifton Rd, CNR 7025, Atlanta, GA 30322 |
| douglas.walker@emory.edu | |
| Phone | (404) 727-6123 |
| Submit Date | 2023-06-19 |
| Num Groups | 2 |
| Total Subjects | 790 |
| Num Females | 790 |
| Study Comments | Samples were collected from participants enrolled in the Shanghai Women's Health Study |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-02-28 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN004513 | AN004514 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | HILIC | Reversed phase |
| Chromatography system | Thermo Dionex Ultimate 3000 RS | Thermo Dionex Ultimate 3000 RS |
| Column | Higgins Analytical TARGA C18 (50 x 2.1mm,5um) | Waters XBridge BEH Amide (50 x 2.1mm,2.5um) |
| 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 | NEGATIVE |
| Units | Peak Intensity | Peak Intensity |
Chromatography:
| Chromatography ID: | CH003390 |
| 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 μL 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: | EmoryUniversity_HRM_DC5min_082016_01.pdf |
| Instrument Name: | Thermo Dionex Ultimate 3000 RS |
| Column Name: | Higgins Analytical TARGA C18 (50 x 2.1mm,5um) |
| Column Temperature: | 40 |
| Flow Gradient: | 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. |
| Flow Rate: | 0.35-0.4 mL/min |
| Solvent A: | 100% water |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | HILIC |
| Solvent C: | 100% water; 2% formic acid |
| Chromatography ID: | CH003391 |
| 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: | EmoryUniversity_HRM_DC5min_082016_01.pdf |
| Instrument Name: | Thermo Dionex Ultimate 3000 RS |
| Column Name: | Waters XBridge BEH Amide (50 x 2.1mm,2.5um) |
| Column Temperature: | 40 |
| Flow Gradient: | 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. |
| Flow Rate: | 0.4-0.5 mL/min |
| Solvent A: | 100% water |
| Solvent B: | 100% acetonitrile |
| Chromatography Type: | Reversed phase |
| Solvent C: | 100% water; 10 mM ammonium acetate |
