Abstract
Backgroundat 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;Methodsthe 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;Resultsa 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;Conclusionsour 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.
Highlights
Bladder cancer (BC) is one of the most common worldwide malignancies
In the attempt to evaluate a possible role of the studied genes in the development and progression of bladder tumors, we compared the transcript levels of human telomerase RNA (hTR), human telomerase reverse transcriptase (hTERT) and CDC28 protein kinase regulatory subunit 2 (CKS2) in exfoliated cells from superficial low grade or muscle invasive high grade bladder cancer (BC) and controls (Table 2)
Regarding hTR, a significant decrement was observed in superficial BC (SBC), becoming more evident in invasive BC (IBC) (Figure 2)
Summary
Bladder cancer (BC) is one of the most common worldwide malignancies. In the Western world it is the fourth most common malignancy among men, following prostate, lung and colon cancers and represents the second most common cause of death among genitourinary tumors [1]. Most human tumours display high levels of telomerase [4,5,6]. Such an expression in cancer cells might be a necessary and essential step for tumor development and progression [6]. Other findings indicate that telomerase expression might not be an obligate requirement in some settings for initial tumor growth, but play an important role for long-term maintenance [7,8]. Further developments indicate that telomere biology knowledge still remains incomplete, and implicate additional complexity in the relationship among telomeres, telomerase and cancer [9]
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