Reduced Expression of Deubiquitinase USP33 Is Associated with Tumor Progression and Poor Prognosis of Gastric Adenocarcinoma

Abstract

BackgroundUbiquitin-specific peptidase 33 (USP33) is a deubiquitinase that balances the ubiquitin status of proteins. It has been reported to act as a tumor suppressor in colorectal cancer and lung cancer. However, the expression pattern and clinical significance of USP33 have not been investigated in gastric adenocarcinoma (GAC).Material/MethodsWe explored the USP33 protein and RNA levels by immunohistochemistry (IHC), Western blot analysis, and qRT-PCR. The Pearson chi-square test was performed to evaluate the statistical associations between USP33 level and patient characteristics. Additionally, the relationship between USP33 expression and patient survival was investigated. Cellular studies, including proliferation assay, migration assay, and invasion assay, were conducted to demonstrate the underlying mechanisms of USP33 in GAC progression.ResultsThis study included 121 patients with GAC. USP33 showed a decreased expression in GAC tissues compared to adjacent normal gastric tissues. Low expression of USP33 was correlated with invasion depth and advanced TNM stage. According to survival analysis, upper location of tumor (P=0.003), invasion depth (P=0.048), advanced TNM stage (P=0.001), and low USP33 level (P=0.001) were all associated with poor overall survival of GAC patients. Cox analysis confirmed the independent role of USP33 in predicting patient survival. Cell experiments showed that USP33 overexpression significantly inhibited the proliferation, migration, and invasion of GAC cells.ConclusionsUSP33 was downregulated in GAC, and was an independent prognostic factor. In vitro results demonstrated the role of USP33 in suppressing tumor progression, suggesting that the developing an agonist of USP33 may be a novel direction for chemotherapy development.

Reduced USP33 expression in gastric cancer decreases inhibitory effects of Slit2‐Robo1 signalling on cell migration and EMT

“…23 However, the precise molecular mechanisms of how USP33 exerts the anti-tumour function in GC remain to be elucidated. 23 However, the precise molecular mechanisms of how USP33 exerts the anti-tumour function in GC remain to be elucidated.…”

Transcriptional characterization of conjunctival melanoma identifies the cellular tumor microenvironment and prognostic gene signatures

“…These results underline the potential of a transcriptional analysis to categorize clinical outcome. While most of the genes predicting outcome of CM have already been described as prognostic factors in other malignancies, such as CENPK [41][42][43][44][45][46] , INHA [47][48][49][50] , RPS6KL1 51 , CASP3 (Caspase 3) 52 , SERPINB1 (Serpin Family B Member 1) 53 , USP33 (Ubiquitin Specific Peptidase 33) [54][55][56][57][58][59] , TRPV4 60 and ACO2 61 , some of the predicting factors have not yet been associated to cancer prognosis, such as GPN1, SNRNP48, AAR2 and SNORA73B. Among the mentioned factors, GPN1 was the gene with the highest correlation coefficient with good clinical outcome in CM.…”

The role of deubiquitinating enzymes in gastric cancer (Review)

“…Studies have also discovered that tumor location, tumor infiltration depth and TNM stage are all associated with USP33 upregulation, and affect the overall survival rate and prognosis of patients with GC. USP33 may also be linked with the prognosis of GC (62), and its high expression levels indicated longer survival times in patients (72).…”