期刊
BRIEFINGS IN BIOINFORMATICS
卷 22, 期 3, 页码 -出版社
OXFORD UNIV PRESS
DOI: 10.1093/bib/bbaa176
关键词
immune checkpoints; expression profile; immunotherapy response; survival analysis
资金
- National Key Research and Development Program of China [2017YFA0700403]
- National Natural Science Foundation of China [31822030, 31801113, 31771458]
- China Postdoctoral Science Foundation [2019M652623, 2018M632830, 2019T120664]
The study identified expression patterns of ICGs and their correlations with patient response to immune checkpoint blockade therapy, providing insights into the mechanisms of ICGs in anticancer treatments. A model using ICG expression features showed robust performance in predicting patient responses and outperformed other mRNA-based predictors.
Immune checkpoint genes (ICGs) play critical roles in circumventing self-reactivity and represent a novel target to develop treatments for cancers. However, a comprehensive analysis for the expression profile of ICGs at a pan-cancer level and their correlation with patient response to immune checkpoint blockade (ICB) based therapy is still lacking. In this study, we defined three expression patterns of ICGs using a comprehensive survey of RNA-seq data of tumor and immune cells from the functional annotation of the mammalian genome (FANTOM5) project. The correlation between the expression patterns of ICGs and patients survival and response to ICB therapy was investigated. The expression patterns of ICGs were robust across cancers, and upregulation of ICGs was positively correlated with high lymphocyte infiltration and good prognosis. Furthermore, we built a model (ICGe) to predict the response of patients to ICB therapy using five features of ICG expression. A validation scenario of six independent datasets containing data of 261 patients with CTLA-4 and PD-1 blockade immunotherapies demonstrated that ICGe achieved area under the curves of 0.64-0.82 and showed a robust performance and outperformed other mRNA-based predictors. In conclusion, this work revealed expression patterns of ICGs and underlying correlations between ICGs and response to ICB, which helps to understand the mechanisms of ICGs in ICB signal pathways and other anticancer treatments.
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