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:
Sample Preparation:
| Sampleprep ID: | SP002886 |
| Sampleprep Summary: | Samples are prepared for metabolomics analysis using established methods (Johnson et al. (2010). Analyst; Go et al. (2015). Tox Sci). Prior to analysis, plasma aliquots were removed from storage at -80°C and thawed on ice. Each cryotube is then vortexed briefly to ensure homogeneity, and 50 μL transferred to a clean microfuge tube. Immediately after, the plasma is treated with 100 μL of ice-cold LC-MS grade acetonitrile (Sigma Aldrich) containing 2.5 μL of internal standard solution with eight stable isotopic chemicals selected to cover a range of chemical properties. Following addition of acetonitrile, plasma is then equilibrated for 30 min on ice, upon which precipitated proteins are removed by centrifuge (16.1 ×g at 4°C for 10 min). The resulting supernatant (100 μL) is removed, added to a low volume autosampler vial and maintained at 4°C until analysis (<22 h). |
| Sampleprep Protocol ID: | EmoryUniversity_HRM_SP_082016_01.pdf |
| Sampleprep Protocol Filename: | EmoryUniversity_HRM_SP_082016_01.pdf |
| Processing Method: | Protein Precipitation with Acetonitrile |
| Processing Storage Conditions: | On ice |
