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| Status |
Public on Apr 27, 2022 |
| Title |
Integrated Metabolic Profiling and Gene Expression Analysis Reveals Therapeutic Modalities in Breast Cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Here, we report two distinctive groups defined by metabolites; a TNBC-HIGH group that shows high levels of pyrimidine pathway metabolites and biosynthetic enzymes, and an ER-HIGH group that shows high levels of fatty acid and arginine biosynthesis intermediates. We identify different metabolic enrichment profiles between cell lines grown in vitro vs. in vivo; cell lines grown in vivo recapitulate patient tumors metabolic profiles. Further, we identify a subset of genes that strongly correlates with the TNBC-HIGH metabolic profile using integrated metabolic and gene expression profiling, which strongly predicts patient prognosis when tested on larger human datasets. As a proof-of-principle, when we target TNBC-HIGH metabolic dysregulation with a pyrimidine biosynthesis inhibitor (Brequinar), and/or a glutaminase inhibitor (CB-839), we observe therapeutic efficacy and decreased tumor growth in representative TNBC cell lines, murine p53-null mammary tumors, and in vivo patient-derived xenografts (PDXs) upon multi-agent drug treatment. This study highlights potential new therapeutic opportunities in breast cancers guided by a genomic biomarker, which could prove impactful for breast cancers that rapidly proliferate.
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| Overall design |
Examination of metabolomics and genomic data for human and murine tumors (in vitro and in vivo) to determine metabolic signatures unqiue to TNBCs vs. other breast cancers.
RNA-Seq raw data is to be made available through dbGaP (controlled access) due to privacy concerns
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| Contributor(s) |
Liao C, Glodowski CR, Fan C, Liu J, Mott KR, Locasale JW, McBrayer SK, DeBerardinis RJ, Perou CM, Zhang Q |
| Citation(s) |
34911787 |
| |
| Submission date |
May 06, 2021 |
| Last update date |
Apr 27, 2022 |
| Contact name |
Charles M. Perou |
| E-mail(s) |
cperou@med.unc.edu
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| Organization name |
University of North Carolina at Chapel Hill
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| Department |
Professor of Genetics, and Pathology & Laboratory Medicine; Lineberger Comprehensive Cancer Center
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| Street address |
12-044 Lineberger Comprehensive Cancer Center CB# 7295
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| City |
Chapel Hill |
| State/province |
NC |
| ZIP/Postal code |
27599-7264 |
| Country |
USA |
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| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA727822 |
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