Journal
ONCOGENE
Volume 39, Issue 3, Pages 587-602Publisher
SPRINGERNATURE
DOI: 10.1038/s41388-019-1002-4
Keywords
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Funding
- National Natural Science Foundation of China [81672440, 31701156, 81502024, 81572881]
- China Postdoctoral Science Foundation [2017M611281]
- Innovation program of science and research from the DICP, CAS [DICP TMSR201601, DICP ZZBS201803]
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Ubiquitin-specific-processing proteases (USPs), the largest deubiquitinating enzyme (DUB) subfamily, play critical roles in cancer. However, clinical utility of USPs is hindered by limited knowledge about their varied and substrate-dependent actions. Here, we performed a comprehensive investigation on pan-cancer impacts of USPs by integrating multi-omics data and annotated data resources, especially a deubiquitination network. Meaningful insights into the roles of 54 USPs in 29 types of cancers were generated. Although rare mutations were observed, a majority of USPs exhibited significant expressional alterations, prognostic impacts and strong correlations with cancer hallmark pathways. Notably, from our DUB-substrate interaction prediction model, additional USP-substrate interactions (USIs) were recognized to complement knowledge gap about cancer-relevant USIs. Intriguingly, expression signatures of the USIs revealed clinically meaningful cancer subtypes, where key USPs and substrates cooperatively contributed to significant prognosis differences among subtypes. Overall, this investigation provides a valuable resource to assist mechanism research and clinical utility about USPs.
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