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Integrated multiomics revealed adenosine signaling predict immunotherapy response and regulate tumor ecosystem of melanoma
- Source :
- Human Genomics, Vol 18, Iss 1, Pp 1-15 (2024)
- Publication Year :
- 2024
- Publisher :
- BMC, 2024.
-
Abstract
- Abstract Extracellular adenosine is extensively involved in regulating the tumor microenvironment. Given the disappointing results of adenosine-targeted therapy trials, personalized treatment might be necessary, tailored to the microenvironment status of individual patients. Here, we introduce the adenosine signaling score (ADO-score) model using non-negative matrix fraction identified patient subtypes using publicly available melanoma dataset, which aimed to profile adenosine signaling-related genes and construct a model to predict prognosis. We analyzed 580 malignant melanoma samples and demonstrated its robust value for prognosis. Further investigation in immune checkpoint inhibitor dataset suggests its potential as a stratified factor of immune checkpoint inhibitor efficacy. We validated the power of the ADO-score at the protein level immunofluorescence in a melanoma cohort from Xiangya Hospital. More importantly, single-cell and spatial transcriptomic data highlighted the cell-specific expression patterns of adenosine signaling-related genes and the existence of adenosine signaling-mediated crosstalk between tumor cells and immune cells in melanoma. Our study reveals a robust connection between adenosine signaling and clinical benefits in melanoma patients and proposes a universally applicable adenosine signaling model, the ADO-score, in gene expression profiles and histological sections. This model enables us to more precisely and conveniently select patients who are likely to benefit from immunotherapy.
Details
- Language :
- English
- ISSN :
- 14797364
- Volume :
- 18
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Human Genomics
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.fa7ae86bfabd4ad595c20006aaa0a822
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s40246-024-00651-3