High Ubiquitin-Specific Protease 2a Expression Level Predicts Poor Prognosis in Upper Tract Urothelial Carcinoma

Appl Immunohistochem Mol Morphol. 2022 Apr 1;30(4):304-310. doi: 10.1097/PAI.0000000000001014.


Background: Ubiquitin-mediated protein degradation has been reported to be involved in regulating the activity of oncoproteins and tumor suppressors. Dysfunction or dysregulation of the ubiquitin-proteasome system may induce tumorigenesis. Deubiquitinase ubiquitin-specific protease 2a (USP2a) has been reported to regulate cell growth or death and is involved in the pathogenesis of various diseases, including cancers. However, the role of USP2a in upper tract urothelial carcinoma (UTUC) has not been investigated yet. The goal of this study was to evaluate the clinical significance of USP2a expression in UTUC.

Materials and methods: A total of 110 UTUC cases were included in this study. USP2a expression level was evaluated through immunohistochemistry staining, and the correlation of USP2a expression level with both clinical and pathologic variables was analyzed.

Results: High USP2a expression level was observed in 48 (43.6%) cancer specimens. USP2a expression level was significantly correlated with tumor stage (P=0.001), grade (P=0.033), and tumor recurrence (P=0.008). High USP2a expression level was correlated with poor disease-free survival (P=0.005) and cancer-specific survival (P<0.001). In addition, high USP2a expression level was an independent predictor of poor disease-free survival (hazard ratio=2.31; P=0.007) and cancer-specific survival (hazard ratio=5.49; P=0.009).

Conclusions: This study indicated that USP2a protein expression level may be a potential biomarker for predicting UTUC patient survival. Further prospective studies are needed to investigate the role of USP2a in UTUC progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Transitional Cell*
  • Humans
  • Neoplasm Recurrence, Local
  • Ubiquitin
  • Ubiquitin Thiolesterase* / genetics
  • Ubiquitin Thiolesterase* / metabolism
  • Ubiquitin-Specific Proteases
  • Urinary Bladder Neoplasms* / metabolism


  • Ubiquitin
  • USP2 protein, human
  • Ubiquitin Thiolesterase
  • Ubiquitin-Specific Proteases