 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 01, 2020 |
| Title |
Development of a gene expression-based prognostic signature for IDH wild-type glioblastoma [AVAglio] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Background. We aimed to develop a gene expression-based prognostic signature for isocitrate dehydrogenase (IDH) wild-type glioblastoma using clinical trial datasets representative of glioblastoma clinical trial populations.
Results. NanoString data were available from 512 patients in the discovery ATE dataset. Elastic net identified a prognostic signature of nine genes (CHEK1, GPR17, IGF2BP3, MGMT, MTHFD1L, PTRH2, SOX11, S100A9, and TFRC). Translating weighted elastic net scores to an average z-score signature conserved the prognostic value of the ATE signature. The z-score signature was prognostic for OS in the ATE dataset (P < 0.0001), as expected, and in the validation cohorts (AVAglio, P < 0.0001; GLARIUS, P = 0.021; UCLA, P = 0.0037). The signature remained prognostic following adjustment for MGMT promoter methylation status or corticosteroid use at baseline. A positive correlation between the signature and proneural/proliferative subtypes was observed in patients with MGMT non-methylated promoter status.
Conclusions. The ATE signature showed prognostic value and may enable clinical trial stratification for IDH wild-type glioblastoma.
|
| |
|
| Overall design |
Methods. Samples were collected from newly diagnosed patients with IDH wild-type glioblastoma in the ARTE, TAMIGA, EORTC 26101 (collectively referred to as ‘ATE’), AVAglio, and GLARIUS trials, or treated at UCLA. Transcriptional profiling was achieved with the NanoString gene expression platform. To identify genes prognostic for overall survival (OS), we built an elastic net Cox-penalized regression model using the ATE dataset for discovery. For validation in independent datasets (AVAglio, GLARIUS, UCLA), we combined elastic net-selected genes into a robust z-score signature to overcome gene expression platform differences between the discovery and validation cohorts.
|
| |
|
| Contributor(s) |
Johnson R, Mancao C, Bourgon R, Garcia J |
| Citation(s) |
32897363 |
| |
| Submission date |
May 14, 2020 |
| Last update date |
Sep 14, 2020 |
| Contact name |
Radia Johnson |
| Organization name |
Genentech
|
| Street address |
1 DNA Way
|
| City |
South San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94080 |
| Country |
United Kingdom |
| |
|
| Platforms (1) |
| GPL28485 |
Genentech glioblastoma custom panel GBM_GNE_C1954 [Gene symbol version] |
|
| Samples (339)
|
|
| This SubSeries is part of SuperSeries: |
| GSE150615 |
Development of a gene expression-based prognostic signature for IDH wild-type glioblastoma |
|
| Relations |
| BioProject |
PRJNA632908 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE150604_RAW.tar |
3.2 Mb |
(http)(custom) |
TAR (of RCC) |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...