TELOMERASE AS A POTENTIAL ONCOMARCER IN THE DEVELOPMENT OF THE NON-INVASIVE DIAGNOSIS OF BLADDER CANCER AT THE EARLY STAGE

DOI: https://doi.org/None

Glukhov A.I., Grigorieva Ya.E., Gordeev S.A., Nalobin D.S., Potoldykova N.V.

Introduction. Among malignant tumors bladder cancer (BC) ranks fifth in the prevalence rate. In the average each year 20% of BC patients die, but in the case of the making diagnosis at the early stages of the disease, survival rate of patients is increasing.Cystoscopyas minimally invasive method appears to be the «Gold standard» of the diagnosticsof BC. Nevertheless the performance of cystoscopy requires a local anesthetic and often gives rise in side effects, whereas currentlyavailable non-invasive methods fail to possess sufficient sensitivity and specificity. The proliferative potential of tumor cells is closely related to the presence of active telomerase. Telomerase activity is detectedby means of TRAP method in 90% of tumors, which makes this marker to be a highly informative in the analysis of cancer pathology. The aim of the study. The analysis of telomerase activity in the operating samples of bladder tissue and cellular urine sedimentations in BC diagnosed patients with the aim of the development of theearly noninvasive diagnosis of BC. Methods. Nonisotopic TRAP method was used for the analysis of telomerase activity in operating bladder tissue samples and cellular urine sedimentations in BC diagnosed patients. Results. There was performed the analysis of the telomerase activity in tumor bladder tissue samples and cellular bladder urine sedimentations of patients with BC and cystitis. At that the telomerase activity was detected as in tumor tissue as well in cellular bladder urine sedimentations of the each BC patient when compared to controls (cystitis). A study of the inhibitory activity of a number of samples on the efficiency of TRAP-assay was performedin order to exclude false negative results. Conclusion. Our results demonstrate the feasibility of non-invasive performance of the diagnosis of BC with the use of TRAP method with sensitivity and specificity of 96 and 100%, respectively.
Keywords: 
bladder cancer, cystitis, telomerase, telomerase activity, non-invasive diagnosis
Список литературы: 
  1. Weikert S.1., Krause H., Wolff I., Christoph F., Schrader M., Emrich T., Miller K., Müller M. Quantitative evaluation of telomerase subunits in urine as biomarkers for noninvasive detection of bladder cancer. Int. J. Cancer. 2005; 117: 274–80.
  2. Black R.J., Bray F., Ferlay J., Parkin D.M. Cancer incidence and mortality in the European Union: cancer registry data and estimates of national incidence for 1990. Eur. J. Cancer. 1997; 33: 1075–9.
  3. Sanchini M.A., Gunelli R., Nanni O., Bravaccini S., Fabbri C., Sermasi A., Bercovich E., Ravaioli A., Amadori D., Calistri D. Relevance of urine telomerase in the diagnosis of bladder cancer. JAMA. 2005; 294 (16): 2052–6.
  4. Muller M. Telomerase: its clinical relevance in the diagnosis of bladder cancer. Oncogene. 2002; 21: 650–5.
  5. Chiodi I., Mondello C. Telomere-independent functions of telomerase in nuclei, cytoplasm, and mitochondria. Frontiers in Oncology. September. 2012; 2 (133): 1–6.
  6. Ulaner G.A., Giudice L.C. Developmental regulation of telomerase activity in human fetal tissues during gestation. Mol. Hum. Reprod. 1997; 3 (9): 769–73.
  7. Mergny J.L., Riou J.F., Mailliet P., Teulade-Fichou M.P., Gilson E. Natural and pharmacological regulation of telomerase. Nucl. Acids Res. 2002; 4: 839–65.
  8. Miker A.K., Koffi D.S. Telomeraza: mnogoobeshhayushhiy marker biologicheskogo bessmertiya polovyh, stvolovyh i rakovyh kletok. Biohimiya. 1997; 62 (11): 1574–1557. [Miker A.K., Koffi D.S. Telomeraza: mnogoobeshhajushhij marker biologicheskogo bessmertija polovyh, stvolovyh i rakovyh kletok. Biohimija. 1997; 62 (11): 1574–1557 (in Russian)]
  9. Sanchini M.A., Bravaccini S., Medri L., Gunelli R., Nanni O., Monti F., Baccarani P.C., Ravaioli A., Bercovich E., Amadori D., Calistri D. Urine telomerase: an important marker in the diagnosis of bladder cancer. Neoplasia. 2004; 6 (3): 234–9.
  10. Lamarca A., Barriuso J. Urine Telomerase for Diagnosis and Surveillance of Bladder Cancer. Advances in Urology. 2012; 2012: 693631.
  11. Raab S.S., Lenel J.C., Cohen M.B. Low grade transitional cell carcinoma of the bladder. Cytologic diagnosis by key features as identified by logistic regression analysis. Cancer. 1994; 74 (5): 1621–6.
  12. Parker J., Spiess P.E. Current and emerging bladder cancer urinary biomarkers. The ScientificWorld J. 2011; 11: 1103–12.
  13. Muller M., Krause H., Heicappell R., Tischendorf J., Shay J.W., Miller K. Comparison of human telomerase RNA and telomerase activity in urine for diagnosis of bladder cancer. Clin Cancer Res. 1998; 4: 1949–51.
  14. Ito H., Kyo S., Kanaya T., Takakura M., Koshida K., Namiki M., Inoue M. Detection of human telomerase reverse transcriptase messenger RNA in voided urine samples as a useful diagnostic tool for bladder cancer. Clin. Cancer Res. 1998; 4: 2807–10.
  15. Hiyama E., Hiyama K. Clinical utility of telomerase in cancer. Oncogene. 2002; 21: 643–9.
  16. Glukhov A.I., Zimnik O.V., Gordeev S.A., Severin S.E. Inhibition of telomerase activity of melanoma cells in vitro by antisense oligonucleotides. Biochem. Biophys. Res. Commun. 1998, 248 (2): 368–71.
  17. Gluhov A.I., Harnas S.S., Ippolitov L.I., Zhulikov D.V., Bochkov I.I, Marchenko I.A. Telomeraza kak potencial`nyy opuholevyy marker v differencial`noy diagnostike novoobrazovaniy shhitovidnoy zhelezy i nadpochechnikov. Annaly hirurgii. 2007; 6: 22–5. [Gluhov A.I., Harnas S.S., Ippolitov L.I., Zhulikov D.V., Bochkov I.I, Marchenko I.A. Telomeraza kak potencial’nyj opuholevyj marker v differencial’noj diagnostike novoobrazovanij shhitovidnoj zhelezy i nadpochechnikov. Annaly hirurgii. 2007; 6: 22–5 (in Russian)]
  18. Svinareva L.V., Glukhov A.I., Zimnik O.V., Bykov I.I., Khorobrykh T.V., Shvets V.I. The study of telomerase activity in gastric cancer. Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry. 2011; 5 (2): 188–92.
  19. Bradford M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 1976; 72: 248–54.
  20. Kim N.W., Piatyszek M.A., Prowse K.R., Harley C.B., West M.D., Ho P.L., Coviello G.M., Wright W.E., Weinrich S.L., Shay J.W. Specific association of human telomerase activity with immortal cells and cancer. Science. 1994; 266 (5193): 2011–5.