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Identification and Validation of Ubiquitin-Specific Proteases as a Novel Prognostic Signature for Hepatocellular Carcinoma. | LitMetric

AI Article Synopsis

  • Ubiquitin-specific proteases (USPs) are linked to the development of various cancers and their roles in hepatocellular carcinoma (HCC) are being studied, but their expression patterns and clinical importance in HCC haven't been thoroughly explored yet.* -
  • Researchers analyzed genomic data to find that overexpression of USPs in HCC tissues was connected to more aggressive cancer characteristics and worse patient outcomes, leading to the identification of a risk signature consisting of eight USPs for predicting HCC prognosis.* -
  • The study confirmed that patients with a high-risk score based on these eight USPs had more advanced tumors and shorter survival times, indicating that the USP signature could serve as a valuable tool for assessing the prognosis of

Article Abstract

Purpose: Ubiquitin-specific proteases (USPs), as a sub-family of deubiquitinating enzymes (DUBs), are responsible for the elimination of ubiquitin-triggered modification. USPs are recently correlated with various malignancies. However, the expression features and clinical significance of USPs have not been systematically investigated in hepatocellular carcinoma (HCC).

Methods: Genomic alterations and expression profiles of USPs were investigated in CbioPortal and The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) dataset. Cox regression and least absolute shrinkage and selection operator (LASSO) analyses were conducted to establish a risk signature for HCC prognosis in TCGA LIHC cohort. Subsequently, Kaplan-Meier analysis, receiver operating characteristic (ROC) curves and univariate/multivariate analyses were performed to evaluate the prognostic significance of the risk signature in TCGA LIHC and international cancer genome consortium (ICGC) cohorts. Furthermore, we explored the alterations of the signature genes during hepatocarcinogenesis and HCC progression in GSE89377. In addition, the expression feature of USP39 was further explored in HCC tissues by performing western blotting and immunohistochemistry.

Results: Genomic alterations and overexpression of USPs were observed in HCC tissues. The consensus analysis indicated that the USPs-overexpressed sub-Cluster was correlated with aggressive characteristics and poor prognosis. Cox regression with LASSO algorithm identified a risk signature formed by eight USPs for HCC prognosis. High-risk group stratified by the signature score was correlated with advanced tumor stage and poor survival HCC patients in TCGA LIHC cohort. In addition, the 8-USPs based signature could also robustly predict overall survival of HCC patients in ICGC(LIRI-JP) cohort. Furthermore, gene sets enrichment analysis (GSEA) showed that the high-risk score was associated with tumor-related pathways. According to the observation in GSE89377, USP39 expression was dynamically increased with hepatocarcinogenesis and HCC progression. The overexpression of USP39 was further determined in a local HCC cohort and correlated with poor prognosis. The co-concurrence analysis suggested that USP39 might promote HCC by regulating cell-cycle- and proliferation- related genes.

Conclusion: The current study provided a USPs-based signature, highlighting its robust prognostic significance and targeted value for HCC treatment.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7949004PMC
http://dx.doi.org/10.3389/fonc.2021.629327DOI Listing

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