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| Status |
Public on Jun 27, 2023 |
| Title |
Drug-class specific gene-based MAPK sensitivity scores predict sensitivity to MAPK inhibitors in pediatric low-grade gliomas |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Pediatric low-grade gliomas (pLGG) have shown heterogeneous responses to MAPK inhibitors (MAPKi) in clinical trials. A predictive feature for stratification is needed to identify patients likely to benefit from MAPKi therapy. MAPK-related genes differentially regulated between MAPKi sensitive and non-sensitive cell lines from the Genomics of Drug Sensitivity in Cancer dataset identified class-specific MAPKi sensitivity gene signatures used to calculate the MAPKi sensitivity score (MSS) via single sample gene set enrichment analysis. The MSS discerned gliomas with varying MAPK alterations from those without, and was higher in pLGG compared to other pediatric CNS tumors. As in clinical trials, the MSS was heterogeneous within pLGGs with a common MAPK alteration. A positive correlation between the MSS and the predicted immune infiltration determined by the ESTIMATE signature was observed. The MSS therefore represents a potential tool for the stratification of pLGG patients, worth of further investigation in upcoming clinical trials. Our data could support a role of microglia in the response to MAPKi, warranting further validation.
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| Overall design |
We examined the single-cell transcriptomes of pLGG tumors from six different patients. For this purpose, single-cell suspensions were prepared from fresh biopsy material, which were then subjected to droplet-based single-cell RNA sequencing (scRNA-seq) using Chromium Next GEM Single Cell 3' Technology by 10x Genomics.
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| Contributor(s) |
Sigaud R, Albert TK, Heß C, Hielscher T, Winkler N, Walter C, Münter D, Selt F, Usta D, Ecker J, Brentrup A, Hasselblatt M, Thomas C, Varghese J, Capper D, Thomale UW, Driever PH, Simon M, Koch A, Sahm F, Hamelmann S, Jabado N, Andrade AF, Schouten-van Meeteren AN, Hoving E, Brummer T, van Tilburg CM, Pfister SM, Witt O, Jones DW, Kerl K, Milde T |
| Citation(s) |
37500667 |
| Submission date |
Jan 13, 2023 |
| Last update date |
Aug 04, 2023 |
| Contact name |
Carolin Walter |
| E-mail(s) |
c_walt03@uni-muenster.de
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| Organization name |
Westfälische Wilhelms-Universität Münster
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| Department |
Medical Faculty of the WWU Münster
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| Lab |
Institute of Medical Informatics
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| Street address |
Domagkstraße 9
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| City |
Münster |
| ZIP/Postal code |
48149 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA923658 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE222850_RAW.tar |
258.6 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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