An integrative pan-cancer analysis of biological and clinical impacts underlying ubiquitin-specific-processing proteases.

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.
Mesh Terms:
Data Mining, Datasets as Topic, Female, Gene Expression Profiling, HEK293 Cells, Humans, Male, Models, Biological, Mutation, Neoplasms, Prognosis, Survival Analysis, Ubiquitin-Specific Proteases, Ubiquitination
Oncogene
Date: Dec. 01, 2019
Download Curated Data For This Publication
228423
Switch View:
  • Interactions 5