Summary of Study ST003221
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 PR002009. The data can be accessed directly via it's Project DOI: 10.21228/M8XJ96 This work is supported by NIH grant, U2C- DK119886. See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST003221 |
| Study Title | Untargeted NMR-lipidomic study in R7, R7sgRON, R7shDEK cells |
| Study Summary | Recurrent and metastatic breast cancer is frequently treatment resistant. A wealth of evidence suggests that reprogrammed lipid metabolism supports cancer recurrence. Overexpression of the RON and DEK proteins in breast cancer is associated with poor outcome. Both proteins promote cancer metastasis in laboratory models, but effects on lipid metabolite levels remain unknown. To measure RON- and DEK-dependent steady-state lipid metabolite levels, an Nuclear Magnetic Resonance (NMR)-based approach was utilized. The observed differences were then used to identify a lipid metabolism-related gene expression signature that is prognostic of overall survival (OS), distant metastasis free survival (DMFS), post-progression survival (PPS), and recurrence free survival (RFS) in patients with breast cancer. RON loss led to decreased cholesterol and sphingomyelin levels, while DEK loss increased total fatty acid levels and decreased free glycerol levels. Lipid-related genes were then queried to define a signature that predicts breast, ovarian, and lung cancer patient survival. Taken together, RON and DEK differentially regulate lipid metabolism in a manner that predicts and may promote breast cancer metastasis and recurrence. |
| Institute | Cincinnati Children's Hospital Medical Center |
| Last Name | Vicente-Munoz |
| First Name | Sara |
| Address | 3333 Burnet Ave |
| Sara.VicenteMunoz@cchmc.org | |
| Phone | 5135172083 |
| Submit Date | 2024-04-30 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | fid |
| Analysis Type Detail | NMR |
| Release Date | 2024-09-12 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR002009 |
| Project DOI: | doi: 10.21228/M8XJ96 |
| Project Title: | NMR-based lipidomics in Breast Cancer |
| Project Summary: | Recurrent and metastatic breast cancer is frequently treatment resistant. A wealth of evidence suggests that reprogrammed lipid metabolism supports cancer recurrence. Overexpression of the RON and DEK proteins in breast cancer is associated with poor outcome. Both proteins promote cancer metastasis in laboratory models, but effects on lipid metabolite levels remain unknown. To measure RON- and DEK-dependent steady-state lipid metabolite levels, an Nuclear Magnetic Resonance (NMR)-based approach was utilized. The observed differences were then used to identify a lipid metabolism-related gene expression signature that is prognostic of overall survival (OS), distant metastasis free survival (DMFS), post-progression survival (PPS), and recurrence free survival (RFS) in patients with breast cancer. RON loss led to decreased cholesterol and sphingomyelin levels, while DEK loss increased total fatty acid levels and decreased free glycerol levels. Lipid-related genes were then queried to define a signature that predicts breast, ovarian, and lung cancer patient survival. Taken together, RON and DEK differentially regulate lipid metabolism in a manner that predicts and may promote breast cancer metastasis and recurrence. |
| Institute: | Cincinnati Children's Hospital Medical Center |
| Last Name: | Vicente-Munoz |
| First Name: | Sara |
| Address: | 3333 Burnet Ave, Cincinnati, OH, 45206, USA |
| Email: | Sara.VicenteMunoz@cchmc.org |
| Phone: | 5135172083 |
Subject:
| Subject ID: | SU003340 |
| Subject Type: | Cultured cells |
| Subject Species: | Mus musculus |
| Taxonomy ID: | 10090 |
| Species Group: | Mammals |
Factors:
Subject type: Cultured cells; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype |
|---|---|---|
| SA352072 | R7-7 | R7 |
| SA352073 | R7-1 | R7 |
| SA352074 | R7-5 | R7 |
| SA352075 | R7-6 | R7 |
| SA352076 | R7-2 | R7 |
| SA352077 | R7-3 | R7 |
| SA352078 | R7-4 | R7 |
| SA352079 | RON-6 | R7sgRON |
| SA352080 | RON-7 | R7sgRON |
| SA352081 | RON-5 | R7sgRON |
| SA352082 | RON-4 | R7sgRON |
| SA352083 | RON-3 | R7sgRON |
| SA352084 | RON-1 | R7sgRON |
| SA352085 | RON-2 | R7sgRON |
| SA352086 | DEK-6 | R7shDEK |
| SA352087 | DEK-7 | R7shDEK |
| SA352088 | DEK-5 | R7shDEK |
| SA352089 | DEK-3 | R7shDEK |
| SA352090 | DEK-1 | R7shDEK |
| SA352091 | DEK-2 | R7shDEK |
| SA352092 | DEK-4 | R7shDEK |
| Showing results 1 to 21 of 21 |
Collection:
| Collection ID: | CO003333 |
| Collection Summary: | Cells were washed three times with ice-cold phosphate-buffered saline, followed by subsequent quenching with ice cold acetonitrile (CH3CN)and the addition of nano-pure water (CH3CN/H2O at 2:1.5 (V/V)) to facilitate cell scraping and collection. |
| Collection Protocol Filename: | BC-SET1-MM.pdf |
| Sample Type: | Breast cancer cells |
Treatment:
| Treatment ID: | TR003349 |
| Treatment Summary: | R7 (control), R7sgRON (RON targeted), R7shDEK (DEK targeted) murine breast cancer cell lines were cultured in complete Dulbecco’s Modified Eagle Medium (DMEM) containing 5% FBS, 1% penicillin-streptomycin, and 0.2% fungizone. R7shDEK were maintained with 1 μg/mL of puromycin for selection. For NMR experiments, cells were seeded in 10 cm-plates in complete DMEM containing 5% dialyzed FBS. |
Sample Preparation:
| Sampleprep ID: | SP003347 |
| Sampleprep Summary: | Dried organic phases (lipids) were reconstituted in 220 µL of 100% methanol-d4 containing 0.05% v/v of tetramethylsilane (TMS) (Cambridge Isotopes Lab. Andover, MA), vortexed and centrifuged at room temperature. 200 µL of the supernatant were transferred into 3 mm NMR tube. |
| Processing Storage Conditions: | On ice |
| Extract Storage: | On ice |
Analysis:
| Analysis ID: | AN005282 |
| Analysis Type: | NMR |
| Analysis Protocol File: | BC-SET1-MM.pdf |
| Num Factors: | 3 |
| Num Metabolites: | 25 |
| Units: | relative abundance |
NMR:
| NMR ID: | NM000283 |
| Analysis ID: | AN005282 |
| Instrument Name: | Bruker Avance III HD 600 MHz spectrometer |
| Instrument Type: | FT-NMR |
| NMR Experiment Type: | 1D-1H |
| Spectrometer Frequency: | 600 MHz |
| NMR Probe: | 5 mm Broad Band Observed (BBO) Prodigy probe |
| NMR Solvent: | MeOD |
| NMR Tube Size: | 3 mm |
| Shimming Method: | Topshim |
| Pulse Sequence: | noesygppr1d |
| Temperature: | 15 |