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S123 Increased expression of UHRF1 gene in urinary bladder cancer
S123
Increased expression of UHRF1 gene in urinary bladder cancer Eur Urol Suppl 2013;12;e1231
Saidi S.1, Popov Z.1, Penev M.1, Stankov O.1, Stavridis S.1, Dohcev S.1, Shabani B.1, Panov S.2 1University
Clinical Complex, University Clinic of Urology, Skopje, Macedonia, 2Faculty of Natural Sciences and Mathematics,
Ss. Cyril and Methodius University, Institute of Biology, Dept. of Molecular Biology and Genetics, Skopje, Macedonia INTRODUCTION & OBJECTIVES: The Ubiquitin-like containing PHD Ring Finger 1 (UHRF1) protein binds to specific DNA sequences, creates a complex with histone deacetylase 1 and DNA methyltransferase 1 and thus regulates gene expression. In addition, UHRF1 downregulate the expression of several tumour suppressor genes including p16INK4A, hMLH1, BRCA1 and RB1 and functions in the p53-dependent DNA damage checkpoint during cell-cycle regulation. This protein is encoded by the UHRF1 gene that seems to have a complex transcription pattern. Recently, expression of the UHRF1 gene was found to be up-regulated in numerous malignant neoplasms, including the urinary bladder transitional cell carcinoma (TCC). The aim of our study was to determine if the expression levels of UHRF1 gene in patients with TCC correlates with the major pathological characteristics of the tumor and patients' clinical outcome. MATERIAL & METHODS: In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). The expression levels were normalized relative to those of the housekeeping gene for β-actin. Obtained data were statistically analyzed regarding the three main clinicopathological parameters: histopathological T-classification grade and stage, as well as the incidence of recidivism, metastasis or cancer-related death during 2-years evaluation period. RESULTS: UHRF1 gene expression was found to be app. 2.5 x higher in samples from patients with TCC in comparison with tissues derived from control group patients (p<0.01). Even more, the obtained gene expression data correlates with the malignancy of the tumor. Namely, highly significant differences were found between the expression values of samples from TCC grade II and III, grade I and III, as well as between the grade III and control group (p<0.01). Furthermore, there was a statistically highly significant difference between the values of muscle-noninvasive (superficial) and muscle-invasive (infiltrative) TCC samples (p<0.01). Similar significance was identified between the UHRF1 expression values in subgroup of patients with TCC that has local recidivism, distant metastasis or death related to cancer during the 2-years follow-up in comparison with the patient's subgroup without those events (p<0.01). CONCLUSIONS: The result of this study indicates that the UHRF1 gene expression levels correlates with major pathological characteristics of TCC samples and clinical outcome of those patients. Determination of expression of UHRF1 gene could have a potential to be used as a very sensitive molecular marker with a considerable prospective value in clinicopathological evaluation and prognosis of patients with urinary bladder cancer.
Increased expression of UHRF1 gene in urinary bladder cancer Eur Urol Suppl 2013;12;e1231
Saidi S.1, Popov Z.1, Penev M.1, Stankov O.1, Stavridis S.1, Dohcev S.1, Shabani B.1, Panov S.2 1University
Clinical Complex, University Clinic of Urology, Skopje, Macedonia, 2Faculty of Natural Sciences and Mathematics,
Ss. Cyril and Methodius University, Institute of Biology, Dept. of Molecular Biology and Genetics, Skopje, Macedonia INTRODUCTION & OBJECTIVES: The Ubiquitin-like containing PHD Ring Finger 1 (UHRF1) protein binds to specific DNA sequences, creates a complex with histone deacetylase 1 and DNA methyltransferase 1 and thus regulates gene expression. In addition, UHRF1 downregulate the expression of several tumour suppressor genes including p16INK4A, hMLH1, BRCA1 and RB1 and functions in the p53-dependent DNA damage checkpoint during cell-cycle regulation. This protein is encoded by the UHRF1 gene that seems to have a complex transcription pattern. Recently, expression of the UHRF1 gene was found to be up-regulated in numerous malignant neoplasms, including the urinary bladder transitional cell carcinoma (TCC). The aim of our study was to determine if the expression levels of UHRF1 gene in patients with TCC correlates with the major pathological characteristics of the tumor and patients' clinical outcome. MATERIAL & METHODS: In our study, we have analyzed the tissue samples derived from group of 70 patients with histologically confirmed TCC of the urinary bladder, while normal urinary bladder mucosa obtained from 40 patients with nonmalignant diseases was used as a negative control group. Expression of UHRF1 gene in each patient sample was determined using reverse transcriptase-polymerase chain reaction (RT-PCR). The expression levels were normalized relative to those of the housekeeping gene for β-actin. Obtained data were statistically analyzed regarding the three main clinicopathological parameters: histopathological T-classification grade and stage, as well as the incidence of recidivism, metastasis or cancer-related death during 2-years evaluation period. RESULTS: UHRF1 gene expression was found to be app. 2.5 x higher in samples from patients with TCC in comparison with tissues derived from control group patients (p<0.01). Even more, the obtained gene expression data correlates with the malignancy of the tumor. Namely, highly significant differences were found between the expression values of samples from TCC grade II and III, grade I and III, as well as between the grade III and control group (p<0.01). Furthermore, there was a statistically highly significant difference between the values of muscle-noninvasive (superficial) and muscle-invasive (infiltrative) TCC samples (p<0.01). Similar significance was identified between the UHRF1 expression values in subgroup of patients with TCC that has local recidivism, distant metastasis or death related to cancer during the 2-years follow-up in comparison with the patient's subgroup without those events (p<0.01). CONCLUSIONS: The result of this study indicates that the UHRF1 gene expression levels correlates with major pathological characteristics of TCC samples and clinical outcome of those patients. Determination of expression of UHRF1 gene could have a potential to be used as a very sensitive molecular marker with a considerable prospective value in clinicopathological evaluation and prognosis of patients with urinary bladder cancer.