Study On The Clinical Value Of Ubiquitin-specific Protease 2 In Clear Cell Renal Cell Carcinoma And Its Functions

ObjectiveTo explore the aberrant expression of ubiquitin-specific protease 2(USP2)in renal clear cell carcinoma(cc RCC)and adjacent normal tissues,and further explore its diagnostic and prognostic value in cc RCC,as well as its biological effect.MethodsWe analyzed datasets from the public database,TCGA,Oncomine,for differential expression of USP2,and further investigated its relationship with the clinical stage,pathological grade and prognosis of renal cancer.We used real-time quantitative PCR and western blot analysis to validate USP2 expression in clinical samples and renal cancer cell lines.Finally,we used CCK-8 and transwell assays to determine its effects on biological functions in cells.OutcomesWe observed significantly lower levels of USP2 m RNA in renal clear cell carcinoma,relative to normal,tissues across the four datasets from the Oncomine database,533 cases from TCGA database and 30 pairs of clinical samples(P<0.001).Similarly,a decreased USP2 protein expression in cc RCC was detected following immunohistochemical(IHC)and western blot analyses.Furthermore,the aberrant expression of USP2 resulted in significant relationship with clinical stage,pathological grade and lower USP2 m RNA expression was interrelated to poor prognosis of renal cell carcinoma.ROC analysis showed that USP2 acted as an important factor for cc RCC diagnosis,with an AUC of 0.8888(95% CI: 0.8529 to 0.9246;P<0.0001).Cell functional experiments showed that exogenous restoration of USP2 in cc RCC cells resulted in repression of cell proliferation,migration,and invasion.ConclusionsOverall,USP2 is significantly downregulated in cc RCC tissue,and the lower the level,the worse the prognosis.USP2 acts as a new biomarker for cc RCC diagnosis and prognosis.Positive modulation of USP2 might lead to development of a novel strategy for cc RCC treatment.