Summary of project PR000730
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
| Project ID: | PR000730 |
| Project DOI: | doi: 10.21228/M89X1C |
| Project Title: | Aspirin Metabolomics in Colorectal Cancer Chemoprevention (part 1 - Colon) |
| Project Type: | NIH/NCI R01CA188038 |
| Project 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: | Clinical Biomarkers Laboratory |
| Last Name: | Uppal |
| First Name: | Karan |
| Address: | 615 Michael Street, Atlanta, GA, 30322, USA |
| Email: | kuppal2@emory.edu |
| Phone: | (404) 727 5027 |
| Funding Source: | NIH/NCI R01CA188038 |
| Project Comments: | Requested embargo date: 8/1/2019 |
| Contributors: | Dartmouth: Elizabeth Barry Leila Mott John Baron Christopher Amos Michael Passarelli Emory: Dean Jones Veronika Fedirko Karan Uppal Shuzhao Li Douglas Walker Yutong Jin Chunyu Ma |
Summary of all studies in project PR000730
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST001091 | Aspirin Metabolomics in Colorectal Cancer Chemoprevention (part 1 - Colon) | Homo sapiens | Emory University | MS* | 2019-09-23 | 1 | 846 | Uploaded data (48.9M) |
| ST001422 | Aspirin Metabolomics in Colorectal Cancer Chemoprevention - blood (part-II) | Homo sapiens | Emory University | MS* | 2020-07-20 | 1 | 692 | Uploaded data (331.3G)* |
| ST001423 | Aspirin Metabolomics in Colorectal Cancer Chemoprevention - blood (part-III) | Homo sapiens | Emory University | MS* | 2020-07-20 | 1 | 494 | Uploaded data (289G)* |
