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.

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Study IDST001405
Study TitleMDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma Models
Study SummaryDedifferentiated 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 NamePatt
First NameAndrew
Address136 W. Pacemont Rd, Columbus, OH, 43202, USA
Emailpatt.14@osu.edu
Phone5183664293
Submit Date2020-05-22
Raw Data AvailableYes
Raw Data File Type(s)mzXML
Analysis Type DetailLC-MS
Release Date2020-07-07
Release Version1
Andrew Patt Andrew Patt
https://dx.doi.org/10.21228/M87X1R
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Project:

Project ID:PR000955
Project DOI:doi: 10.21228/M87X1R
Project Title:MDM2-Dependent Rewiring of Metabolomic and Lipidomic Profiles in Dedifferentiated Liposarcoma(DDLPS) Models
Project 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:Andrew Patt
First Name:Andrew Patt
Address:136 W. Pacemont Rd, Columbus, OH, 43202, USA
Email:patt.14@osu.edu
Phone:518-366-4293

Subject:

Subject ID:SU001479
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606

Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Treatment_Status MDM2 Amplification Cell line
SA114059LIPNEG17MAR_56.10Atorvastatin Higher 141
SA114060LIPNEG17MAR_16.12Atorvastatin Higher 141
SA114061LIPPOS17MAR_56.10Atorvastatin Higher 141
SA114062LIPNEG17MAR_69.11Atorvastatin Higher 141
SA114063LIPPOS17MAR_16.12Atorvastatin Higher 141
SA114064LIPPOS17MAR_69.11Atorvastatin Higher 141
SA114065LIPNEG17MAR_60.84Atorvastatin Higher 224A
SA114066LIPPOS17MAR_60.84Atorvastatin Higher 224A
SA114067LIPPOS17MAR_04.83Atorvastatin Higher 224A
SA114068LIPPOS17MAR_77.82Atorvastatin Higher 224A
SA114069LIPNEG17MAR_83.83Atorvastatin Higher 224A
SA114070LIPNEG17MAR_77.82Atorvastatin Higher 224A
SA114071LIPNEG17MAR_33.47Atorvastatin Higher 246
SA114072LIPPOS17MAR_31.46Atorvastatin Higher 246
SA114073LIPPOS17MAR_33.47Atorvastatin Higher 246
SA114074LIPNEG17MAR_31.46Atorvastatin Higher 246
SA114075LIPNEG17MAR_59.48Atorvastatin Higher 246
SA114076LIPPOS17MAR_59.48Atorvastatin Higher 246
SA114077LIPNEG17MAR_32.119Atorvastatin Lower 224B
SA114078LIPPOS17MAR_15.118Atorvastatin Lower 224B
SA114079LIPPOS17MAR_76.120Atorvastatin Lower 224B
SA114080LIPNEG17MAR_15.118Atorvastatin Lower 224B
SA114081LIPNEG17MAR_76.120Atorvastatin Lower 224B
SA114082LIPPOS17MAR_32.119Atorvastatin Lower 224B
SA114083LIPNEG17MAR_57.155Atorvastatin Lower 815
SA114084LIPPOS17MAR_37.154Atorvastatin Lower 815
SA114085LIPPOS17MAR_58.156Atorvastatin Lower 815
SA114086LIPNEG17MAR_58.156Atorvastatin Lower 815
SA114087LIPPOS17MAR_57.155Atorvastatin Lower 815
SA114088LIPNEG17MAR_37.154Atorvastatin Lower 815
SA114089LIPPOS17MAR_11.191Atorvastatin Lower 863
SA114090LIPNEG17MAR_39.192Atorvastatin Lower 863
SA114091LIPPOS17MAR_39.192Atorvastatin Lower 863
SA114092LIPNEG17MAR_40.190Atorvastatin Lower 863
SA114093LIPPOS17MAR_40.190Atorvastatin Lower 863
SA114094LIPNEG17MAR_11.191Atorvastatin Lower 863
SA114095LIPPOS17MAR_63.POOL.4N/A N/A N/A
SA114096LIPPOS17MAR_81.BLANK.5N/A N/A N/A
SA114097LIPPOS17MAR_82.POOL.5N/A N/A N/A
SA114098LIPPOS17MAR_62.BLANK.4N/A N/A N/A
SA114099LIPPOS17MAR_20.BLANK.2N/A N/A N/A
SA114100LIPPOS17MAR_42.BLANK3N/A N/A N/A
SA114101LIPPOS17MAR_43.POOL.3N/A N/A N/A
SA114102LIPPOS17MAR_21.POOL.2N/A N/A N/A
SA114103LIPPOS17MAR_02.POOL.1N/A N/A N/A
SA114104LIPPOS17MAR_01.BLANK.1N/A N/A N/A
SA114105LIPNEG17MAR_42.BLANK3N/A N/A N/A
SA114106LIPNEG17MAR_43.POOL.3N/A N/A N/A
SA114107LIPNEG17MAR_01.BLANK.1N/A N/A N/A
SA114108LIPNEG17MAR_62.BLANK.4N/A N/A N/A
SA114109LIPNEG17MAR_63.POOL.4N/A N/A N/A
SA114110LIPNEG17MAR_89.BLANK.5N/A N/A N/A
SA114111LIPNEG17MAR_02.POOL.1N/A N/A N/A
SA114112LIPNEG17MAR_90.POOL.5N/A N/A N/A
SA114113LIPNEG17MAR_21.POOL.2N/A N/A N/A
SA114114LIPNEG17MAR_20.BLANK.2N/A N/A N/A
SA114115LIPPOS17MAR_52.3Untreated Higher 141
SA114116LIPNEG17MAR_52.3Untreated Higher 141
SA114117LIPPOS17MAR_47.1Untreated Higher 141
SA114118LIPPOS17MAR_71.2Untreated Higher 141
SA114119LIPNEG17MAR_47.1Untreated Higher 141
SA114120LIPNEG17MAR_71.2Untreated Higher 141
SA114121LIPPOS17MAR_12.74Untreated Higher 224A
SA114122LIPPOS17MAR_30.75Untreated Higher 224A
SA114123LIPPOS17MAR_07.73Untreated Higher 224A
SA114124LIPNEG17MAR_07.73Untreated Higher 224A
SA114125LIPNEG17MAR_12.74Untreated Higher 224A
SA114126LIPNEG17MAR_30.75Untreated Higher 224A
SA114127LIPPOS17MAR_09.38Untreated Higher 246
SA114128LIPNEG17MAR_27.37Untreated Higher 246
SA114129LIPPOS17MAR_27.37Untreated Higher 246
SA114130LIPNEG17MAR_09.38Untreated Higher 246
SA114131LIPNEG17MAR_84.39Untreated Higher 246
SA114132LIPPOS17MAR_05.39Untreated Higher 246
SA114133LIPNEG17MAR_53.109Untreated Lower 224B
SA114134LIPPOS17MAR_25.110Untreated Lower 224B
SA114135LIPNEG17MAR_10.111Untreated Lower 224B
SA114136LIPNEG17MAR_25.110Untreated Lower 224B
SA114137LIPPOS17MAR_10.111Untreated Lower 224B
SA114138LIPPOS17MAR_53.109Untreated Lower 224B
SA114139LIPPOS17MAR_51.145Untreated Lower 815
SA114140LIPPOS17MAR_72.147Untreated Lower 815
SA114141LIPNEG17MAR_72.147Untreated Lower 815
SA114142LIPNEG17MAR_51.145Untreated Lower 815
SA114143LIPNEG17MAR_18.146Untreated Lower 815
SA114144LIPPOS17MAR_18.146Untreated Lower 815
SA114145LIPPOS17MAR_38.183Untreated Lower 863
SA114146LIPNEG17MAR_70.182Untreated Lower 863
SA114147LIPPOS17MAR_67.181Untreated Lower 863
SA114148LIPNEG17MAR_38.183Untreated Lower 863
SA114149LIPPOS17MAR_70.182Untreated Lower 863
SA114150LIPNEG17MAR_67.181Untreated Lower 863
Showing results 1 to 92 of 92

Collection:

Collection ID:CO001474
Collection Summary:Cells were collected using 1mL of cold (-20C) methanol and a cell scraper and then immediately stored at -80C.
Sample Type:Cultured cells

Treatment:

Treatment ID:TR001494
Treatment Summary:DDLPS were plated in 60mm dishes and drug treated with atorvastatin for 72 hours.All cells were cultured in Dulbecco's modified Eagle's medium (DMEM) and supplemented with 10\% fetal bovine serum (FBS), 100 U/mL penicillin, and 100 U/mL streptomycin. These cells were cultured in a humidified chamber delivering 5% CO2 at 37 degrees C.
Treatment Compound:Atorvastatin
Cell Media:Dulbecco's modified Eagle's medium

Sample Preparation:

Sampleprep ID:SP001487
Sampleprep Summary:Cells were pelleted and processed using a chloroform:methanol homogenization followed by an isoproponal:acetonitrile extraction. 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.
Processing Storage Conditions:-80℃
Extract Storage:-80℃

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 Triple TOF Triple TOF
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

MS:

MS ID:MS002189
Analysis ID:AN002347
Instrument Name:ABI Sciex 5600 TripleTOF
Instrument Type:Triple TOF
MS Type:ESI
MS Comments:The capillary voltage was set at 5.5 kV, with a declustering potential of 80V. The mass spectrometer was operated in IDA (Information Dependent Acquisition) mode with a 100 ms survey scan from 100 to 1200 m/z, and up to 20 MS/MS product ion scans (100 ms) per duty cycle using a collision energy of 50V with a 20V spread.
Ion Mode:POSITIVE
  
MS ID:MS002190
Analysis ID:AN002348
Instrument Name:ABI Sciex 5600 TripleTOF
Instrument Type:Triple TOF
MS Type:ESI
MS Comments:The capillary voltage was set at 4.5 kV, with a declustering potential of 80V. The mass spectrometer was operated in IDA (Information Dependent Acquisition) mode with a 100 ms survey scan from 100 to 1200 m/z, and up to 20 MS/MS product ion scans (100 ms) per duty cycle using a collision energy of 50V with a 20V spread.
Ion Mode:NEGATIVE
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