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Status |
Public on Apr 15, 2024 |
Title |
Determinants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci |
Organism |
Homo sapiens |
Experiment type |
Other
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Summary |
Only a portion of cancer patients respond favorably to immunotherapy, indicating the need for new biomarkers and targets. Here, we identify common somatic and germline 3´ untranslated region (3´UTR) variants across the human transcriptome from 375 gastric cancer patients from The Cancer Genome Atlas (39.5% somatic). By performing gene expression quantitative trait loci (eQTL) and immune landscape QTL (ilQTL) analysis, we discover 3´UTR variants with cis effects on expression and immune landscape phenotypes, such as immune cell infiltration. To distinguish between causal and correlative effects of 3´UTR eQTLs in immune-related genes, we perform a massively parallel reporter assay. Our approach identifies numerous 3´UTR eQTLs and ilQTLs (e.g. in ADAR1), providing a unique resource for the identification of immunotherapeutic targets and biomarkers. Our prioritized ilQTL variant signature predicts response to immunotherapy better than standard-of-care PD-L1 expression in independent patient cohorts, showcasing the untapped potential of non-coding mutations in cancer.
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Overall design |
To assess the effect of 3'UTR variants on gene expression we performed a massively parallel reporter assay (MPRA) in two stomach cancer cell lines (AGS, SNU719) in triplicate.
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Contributor(s) |
Miliotis C, Karagkouni D, Mattioli K, Slack FJ, Vlachos IS |
Citation(s) |
38773080 |
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Submission date |
Mar 15, 2024 |
Last update date |
Jun 05, 2024 |
Contact name |
Christos Miliotis |
E-mail(s) |
cnmiliotis@gmail.com
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Organization name |
BIDMC
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Department |
Cancer Center
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Street address |
330 Brookline Ave
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City |
Boston |
State/province |
MA |
ZIP/Postal code |
02215 |
Country |
USA |
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Platforms (1) |
GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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Samples (7)
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Relations |
BioProject |
PRJNA1088465 |
Supplementary file |
Size |
Download |
File type/resource |
GSE261709_RAW.tar |
690.0 Kb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
Raw data are available in SRA |
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