 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Sep 02, 2015 |
| Title |
Spinal Ependymoma Gene Expression Data |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Purpose: Myxopapillary ependymoma (MPE) is a distinct histological variant of ependymoma arising commonly in the spinal cord. Despite an overall favorable prognosis, distant metastases, subarachnoid dissemination, and late recurrences have been reported. Currently the only effective treatment for MPE is gross-total resection. We characterized the genomic and transcriptional landscape of spinal ependymomas in an effort to delineate the genetic basis of this disease and identify new leads for therapy.
Experimental Design: Gene expression profiling was performed on 35 spinal ependymomas. Functional validation experiments were performed on tumour lysates consisting of assays measuring Pyruvate Kinase M activity (PKM), Hexokinase activity (HK), and lactate production.
Results: At a gene expression level, we demonstrate that spinal Grade II and MPE are molecularly and biologically distinct. These findings are supported by specific copy number alterations occurring in each histological variant. Pathway analysis revealed that MPE are characterized by increased cellular metabolism, associated with up-regulation of HIF-1α. These findings were validated by western blot analysis demonstrating increased protein expression of HIF-1α, HK2, PDK1, and phosphorylation of PDHE1A. Functional assays were performed on MPE lysates, which demonstrated decreased PKM activity, increased HK activity, and elevated lactate production.
Conclusions: Our findings suggest that MPE may be driven by a Warburg metabolic phenotype. The key enzymes promoting the Warburg phenotype: HK2, PKM2, and PDK are targetable by small molecule inhibitors/activators, and should be considered for evaluation in future clinical trials for MPE.
|
| |
|
| Overall design |
RNA from 35 primary spinal ependymomas (fresh frozen) were isolated by pulverization in liquid nitrogen, and extraction using the Trizol Method (Invitrogen) [PMID:21840481]
|
| |
|
| Contributor(s) |
Mack SC, Taylor MD |
| Citation(s) |
25957288 |
| |
| Submission date |
Mar 11, 2015 |
| Last update date |
Nov 08, 2016 |
| Contact name |
Stephen Mack Christopher |
| E-mail(s) |
[email protected]
|
| Phone |
2163182292
|
| Organization name |
Baylor College of Medicine
|
| Department |
Pediatrics
|
| Lab |
Stephen Mack Lab
|
| Street address |
1102 Bates Avenue C1030.02
|
| City |
Houston |
| State/province |
TX |
| ZIP/Postal code |
770030 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
|
| Samples (35)
|
|
| Relations |
| BioProject |
PRJNA277960 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66787_RAW.tar |
154.3 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...