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

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.

Nuclear Matrix Protein-22 and Telomerase Reverse Transcriptase Are Diagnostic Markers for Bladder Carcinoma in Egypt

“…Previous reports have pointed out that telomerase activity as well as the mRNA expression levels of its subunits is associated with malignancy in many bladder tumor histotypes [24][25][26][27][28], which is in line with our results on Egyptian bladder cancer patients. Additionally, and in agreement with our results, Mezzasoma et al reported 11.4 fold increment of hTERT expression in washing fluids of bladder cancer patients compared to controls, reflecting the necessity in producing high levels of proteins required for its biological function [29]. Moreover, Li et al showed that telomerase activity in urine was helpful in diagnosis of urothelial carcinomas and may be related to degree of differentiation [30].…”

“…Recent study by Eissa et al reported that hTERT showed significant difference between bladder cancer, benign bladder lesions, and healthy individuals (p < 0.001) [31]. Former studies reported that expression of hTERT and hTR mRNA, in voided urine samples, seems to correlate positively with tumor stage and grade [24,29,32]. Here we reported that urinary levels of hTERT positively correlated with that of NMP-22 in both bladder cancer group and transitional cell bladder carcinoma group, but not in squamous cell bladder carcinoma, in line with Abd El Gawad et al [33].…”

Serum human telomerase reverse transcriptase: a novel biomarker for breast cancer diagnosis

“…hTERT represents the major determinant of telomerase activity and is one of the most attractive molecular markers available, promising a target spectrum of approximately 85% of all tumors [14]. In addition, a number of previous studies have demonstrated that hTERT is frequently found in the plasma, serum and washing fluids of cancer patients [15][16][17][18][19]. hTERT expression enhances the chemo-resistance of cancer cells, and effective therapies are associated with decreased expression of hTERT, so imaging of hTERT expression also has prognostic value [20].…”

Bladder Cancer Markers and Recent Innovations

“…It keeps intact chromosomes adding telomeres at the ends chromosomes, lengthening again the shortened telomeres. In normal cells it is active only during embryonic development while in most normal adult tissues its expression is repressed [84]. The expression of telomerase in tumor cells immortalize them [85].…”

“…The expression of telomerase in tumor cells immortalize them [85]. This mechanism can be considered a crucial step in tumorigenesis [84].…”