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| Status |
Public on Mar 18, 2016 |
| Title |
mRNA expressions in pre-treatment melanomas undergoing anti-PD-1 checkpoint inhibition therapy |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
PD-1 immune checkpoint blockade provides significant clinical benefits for cancer patients. However, factors influencing innate sensitivity remain incompletely catalogued. We analyzed the somatic mutanomes and transcriptomes of pretreatment melanoma biopsies. Mutations in cell adhesion genes and the DNA repair gene BRCA2 were enriched in responding tumors, and a high mutational load associated with improved survival. Innately resistant tumors displayed frequent transcriptomic up-expression of genes that enriched for mesenchymal transition, cell adhesion, ECM organization, wound-healing and angiogenesis. The transcriptomes of innate resistance also enriched for signatures indicating up-regulation of these processes. Notably, MAPK-targeted therapy (MAPKi) induced similar signatures in melanoma, suggesting that a form of MAPKi resistance mediates cross-resistance to anti-PD-1 therapy. Co-enrichment of IPRIM (Innate anti-PD-1 Resistance Induced by MAPKi) signatures defined a transcriptomic subset across advanced cancers, suggesting that attenuating processes underlying these signatures may augment anti-PD1 responses. Thus, multi-factorial determinants influence anti-PD-1 patterns in melanoma.
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| Overall design |
Melanoma biopsies pre-anti-PD-1 therapy were sent for transcriptomic analysis by paired-end RNAseq analysis to find the correlates of response vs. non-response to the therapy
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| Contributor(s) |
Hugo W, Zaretsky JM, Sun L, Song C, Homet-Moreno B, Hu-Lieskovan S, Berent-Maoz B, Pang J, Chmielowski B, Cherry G, Seja E, Lomeli S, Kong X, Kelley MC, Sosman JA, Johnson DB, Ribas A, Lo RS |
| Citation(s) |
26997480 |
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| Submission date |
Feb 23, 2016 |
| Last update date |
Dec 08, 2021 |
| Contact name |
Willy Hugo |
| E-mail(s) |
hwilly@mednet.ucla.edu
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| Organization name |
UCLA
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| Department |
Medicine
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| Street address |
10833 Le Conte Ave, 52-121 CHS, Division of Dermatology
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| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90095 |
| Country |
USA |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (28)
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| Relations |
| BioProject |
PRJNA312948 |
| SRA |
SRP070710 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE78220_PatientFPKM.xlsx |
6.8 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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