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

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Ubiquitin-specific-processing proteases (USPs) are the largest deubiquitinating enzyme (DUB) subfamily and are implicated in cancer development.
• The clinical application of USPs is limited by incomplete understanding of their diverse and substrate-specific functions in cancer.

Purpose of the Study:

• To comprehensively investigate the pan-cancer impacts of USPs.
• To identify novel USP-substrate interactions (USIs) and their clinical relevance.
• To provide a resource for USP-related cancer research and clinical utility.

Main Methods:

• Integration of multi-omics data and annotated resources, including a deubiquitination network.
• Analysis of USP expression alterations, mutations, and prognostic impacts across 29 cancer types.
• Development of a DUB-substrate interaction prediction model to identify novel USIs.

Main Results:

• Significant expressional alterations and prognostic impacts were observed for most of the 54 studied USPs across 29 cancer types.
• A DUB-substrate interaction prediction model identified additional cancer-relevant USIs, addressing knowledge gaps.
• USP-substrate interaction signatures revealed clinically meaningful cancer subtypes with distinct prognoses.

Conclusions:

• This study offers valuable insights into the roles of USPs in various cancers.
• The identified USIs and cancer subtypes can aid in understanding USP mechanisms and developing targeted therapies.
• The findings provide a foundation for advancing the clinical utility of USPs in oncology.