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Background  at present, pathogenesis of bladder cancer (BC) has not been fully elucidated. Aim of this study is to investigate the role of human telomerase RNA ( hTR ), human telomerase reverse transcriptase ( hTERT ) and CDC28 protein kinase regulatory subunit 2 ( CKS2 ) in bladder carcinogenesis and their possible clinical significance;    Methods  the transcript levels of  hTR ,  hTERT  and  CKS2  were quantified by Real time reverse transcriptase chain reaction in exfoliated cells from bladder washings of 36 patients with BC and 58 controls. The statistical significance of differences between BC bearing patients and control groups, in the general as well as in the stratified analysis (superficial or invasive BC), was assessed by Student's t test. Non parametric Receiver Operating Characteristics analysis (ROC) was performed to ascertain the accuracy of study variables to discriminate between BC and controls. The clinical value of concomitant examination of  hTR ,  hTERT  and  CKS2  was evaluated by logistic regression analysis;    Results  a significant decrease in  hTR  and a significant increase in  hTERT  or  CKS2  gene expression were found between BC bearing patients and controls, as well as in the subgroups analysis. The area under the curve (AUC) indicated an average discrimination power for the three genes, both in the general and subgroups analysis, when singularly considered. The ability to significantly discriminate between superficial and invasive BC was observed only for  hTR  transcript levels. A combined model including  hTR  and  CKS2  was the best one in BC diagnosis;    Conclusions  our results, obtained from a sample set particularly rich of exfoliated cells, provide further molecular evidence on the involvement of  hTR, hTERT  and  CKS2  gene expression in BC carcinogenesis. In particular, while  hTERT  and  CKS2  gene expression seems to have a major involvement in the early stages of the disease,  hTR  gene expression, seems to be more involved in progression. In addition, our findings suggest that the studied genes have a clinical role in discriminating between BC and controls in the general as well as in the stratified analysis, when singularly considered. A combined model improved over the single marker BC diagnosis.

Expression and biological-clinical significance of hTR, hTERT and CKS2 in washing fluids of patients with bladder cancer