Summary of Study ST001405
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 PR000955. The data can be accessed directly via it's Project DOI: 10.21228/M87X1R 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 | ST001405 |
| Study Title | MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models |
| Study Summary | Dedifferentiated liposarcoma (DDLPS) is an aggressive mesenchymal cancer marked by amplification of MDM2, an inhibitor of the tumor suppressor TP53. DDLPS patients with higher MDM2 amplification have lower chemotherapy sensitivity and worse outcome than patients with lower MDM2 amplification. We hypothesized that MDM2 amplification levels may be associated with changes in DDLPS metabolism. Six patient-derived DDLPS cell line models were subject to comprehensive metabolomic (Metabolon) and lipidomic (SCIEX 5600 TripleTOF-MS) profiling to assess associations with MDM2 amplification and their responses to metabolic perturbations. Comparing metabolomic profiles between MDM2 higher and lower amplification cells yielded a total of 23 differentially abundant metabolites across both panels (FDR < 0.05, log2 FC < 0.75), including ceramides, glycosylated ceramides, and sphingomyelins. Disruption of lipid metabolism through statin administration resulted in a chemo-sensitive phenotype in MDM2 lower cell lines only, suggesting that lipid metabolism may be a large contributor to the more aggressive nature of MDM2 higher DDLPS tumors. This study is the first to provide comprehensive metabolomic and lipidomic characterization of DDLPS cell lines and provides evidence for MDM2-dependent differential molecular mechanisms that are critical factors in chemoresistance and could thus affect patient outcome. |
| Institute | The Ohio State University |
| Last Name | Patt |
| First Name | Andrew |
| Address | 136 W. Pacemont Rd, Columbus, OH, 43202, USA |
| patt.14@osu.edu | |
| Phone | 5183664293 |
| Submit Date | 2020-05-22 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | mzXML |
| Analysis Type Detail | LC-MS |
| Release Date | 2020-07-07 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Combined analysis:
| Analysis ID | AN002347 | AN002348 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Shimadzu Prominence 20 UFLCXR | Shimadzu Prominence 20 UFLCXR |
| Column | Waters XBridge C18 (50 x 2.1mm,3um) | Waters XBridge C18 (50 x 2.1mm,3um) |
| MS Type | ESI | ESI |
| MS instrument type | QTOF | QTOF |
| MS instrument name | ABI Sciex 5600 TripleTOF | ABI Sciex 5600 TripleTOF |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | ppm | ppm |
Chromatography:
| Chromatography ID: | CH001720 |
| Chromatography Summary: | Samples were separated by reverse phase HPLC using a Prominence 20 UFLCXR system (Shimadzu, Columbia MD) with a Waters (Milford, MA) CSH C18 column (100mm x 2.1mm 1.7 um particle size) maintained at 55C and a 20 minute aqueous/acetonitrile/isopropanol gradient, at a flow rate of 225 ul/min. For electrospray ionization positive mode, Solvent A was 40% water, 60% acetonitrile with 10mM ammonium formate and 0.1% formic acid, and Solvent B was 90% isopropanol, 10% acetonitrile with 10mM ammonium formate and 0.1% formic acid. For electrospray ionization negative mode, Solvent A was 40% water, 60% isopropanol with 10 mM ammonium acetate, and solvent B was 90% isopropanol, 10% acetonitrile with 10 mM ammonium acetate. The initial conditions were 60% A and 40% B, increasing to 43% B at 2 minutes, 50% B at 2.1 minutes, 54% B at 12 minutes, 70% B at 12.1 minutes and 99% B at 18 minutes, held at 99% B until 20.0 minutes before returning to the initial conditions. |
| Instrument Name: | Shimadzu Prominence 20 UFLCXR |
| Column Name: | Waters XBridge C18 (50 x 2.1mm,3um) |
| Column Temperature: | 55 |
| Flow Gradient: | The initial conditions were 60% A and 40% B, increasing to 43% B at 2 minutes, 50% B at 2.1 minutes, 54% B at 12 minutes, 70% B at 12.1 minutes and 99% B at 18 minutes, held at 99% B until 20.0 minutes before returning to the initial conditions. |
| Flow Rate: | 225 ul/min |
| Solvent A: | Pos mode: 40% water/60% acetonitrile; 0.1% formic acid; 10mM ammonium formate, Neg mode: 40% water/60% isopropanol; 10 mM ammonium acetate |
| Solvent B: | Pos mode: 90% isopropanol/10% acetonitrile; 0.1% formic acid; 10mM ammonium formate, Neg mode: 90% isopropanol/10% acetonitrile; 10 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
