Diagnostic Performances of Urine Cytology and TERT Promoter Mutations in Bladder Cancer
Main Article Content
Keywords
Urine, Bladder cancer, TERT mutations, recurrence, survival time.
Abstract
Background: Detecting bladder cancer (BC) using urinary biomarkers may provide a valuable opportunity for screening and management. The best hope for reducing bladder cancer mortality and morbidity remains early detection. Two hotspot mutations in the promoter region of the C228T and C250T, are frequently found in several tumor types, and considered as an early event in BC tumorigenesis. This study aims to assess the validity and diagnostic potential of these mutations to detect BC in urine tDNA-based liquid biopsy in patients and evaluate the expression of NMP-22 and MMP-9 in the urine of patients and controls, analyze the diagnostic efficacy of them and to examine their expression in relation to the TERT mutant and wild patients.
Methods & Results: 210 BC patients and 95 healthy volunteers served as controls were screened for TERT promoter mutations by PCR from urine samples, in addition to Enzyme-Linked Immunosorbent Assay (ELISA) detection for NMP-22 and MMP-9 levels, a significant increase in the expression level of NMP-22 and MMP-9 was detected indicating a significant diagnostic capability for BC, and was higher for TERT mutant variants. 141 patients (67.1%) were identified to harbor C228T TERT promoter mutations, while C250T was detected in 64 patients (30.4%). Univariate logistic regression analysis revealed that the 2 mutations were statistically associated with BC, in addition to an association with high grades, tumor recurrence and invasiveness.
Conclusion: Detection of TERT promoter mutations in urine could present a reliable noninvasive diagnostic marker for BC, with patient survival time, disease recurrence and invasiveness as a unique predictor marker with individualized prognostic potential.
References
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35. Hayashi Y, Fujita K, Netto GJ, et al (2021) Clinical Application of TERT Promoter Mutationsin Urothelial Carcinoma. Front Oncol, 11, 705440.
doi:10.3389/fonc.2021.705440
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MUDASARLOVA RESERVOIR OF VISAKHAPATNAM, INDIA . Journal Of Advanced Zoology, 42(02), 165–175. https://doi.org/10.17762/jaz.v42i02.51
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39. Wankhade, L. N. . (2022). STUDY ON BUTTERFLY FAUNA OF KARANJA (GHADGE) TAHSIL OF DISTRICT WARDHA
(MAHARASHTRA). Journal Of Advanced Zoology, 42(02), 186–193. https://doi.org/10.17762/jaz.v42i02.53
40. Descotes F, Kara N, Decaussin-Petrucci M et al (2017) Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT
promoter mutations in urine. Br J Cancer, 117(4), 583-587. doi:10.1038/bjc.2017.210
41. Rachakonda PS, Hosen I, de Verdier PJ et al (2013) TERT promoter mutations in bladder cancer affect patient survival and disease
recurrence through modification by a common polymorphism. Proc Natl Acad Sci U S A, 110(43), 17426-17431. doi:10.1073/pnas.1310522110
42. de Kouchkovsky I, Zhang L, Philip EJ et al (2021) TERT promoter mutations and other prognostic factors in patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor. Immunother Cancer, 9(5). doi:10.1136/jitc-2020-002127
43. Faisal, H. T. ., Abid, M. K. ., & Abed, A. . (2022). Study Of Some Biochemical Parameters in Dose During Pregnancy in Goats. Journal Of Advanced Zoology, 43(1), 01–06. https://doi.org/10.17762/jaz.v43i1.109
44. Gulati, H. ., & Rana, S. . (2022). Habitat Preference and Current Threats to The Sarus Cranes Grus Antigone (Aves: Gruiformes:
Gruidae) In Important Bird Areas of Haryana, India: Implications for Determining Effective Conservation Actions. Journal Of Advanced
Zoology, 43(1), 07–16. Retrieved from http://jazindia.com/index.php/jaz/article/view/110
45. Mokhtar, A. R. R. A. S. . (2022). Development Of Saponin Based Wettable Powder Formulation from Phaleria macrocarpa To Control Pomacea maculate. Journal Of Advanced Zoology, 43(1), 17–31. Retrieved from http://jazindia.com/index.php/jaz/article/view/111
pilot study. Mol Clin Oncol, 15(6), 253. doi:10.3892/mco.2021.2415
2. Mohammadian M, Safari A, Bakeshei KA, et al(2020) Recent patterns of bladder cancer incidence and mortality: A global overview. World Cancer Res 7: e1464.
3. Das S, Hayden J, Sullivan T et al (2023)The Roles of miRNAs in Predicting Bladder Cancer Recurrence and Resistance to Treatment.
International Journal of Molecular Sciences.24(2):964. https://doi.org/10.3390/ijms24020964.
4. Amy KK, Selena YL, Surbhi J et al (2021) Urine as a non-invasive alternative to blood for germline and somatic mutation detection in hepatocellular carcinoma. doi:https://doi.org/10.1101/2021.12.03.21266943.
5. Broughton EI, Gooden KM, Mycock KL et al (2022) Multi-country clinical practice patterns, including use of biomarkers, among physicians'
treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). BMC Urol, 22(1), 27. doi:10.1186/s12894-022-00959-z
6. Lopez-Cortes R, Vazquez-Estevez S, Fernandez JA (2021) Proteomics as a Complementary Technique to Characterize Bladder Cancer.
Cancers (Basel), 13(21). doi:10.3390/cancers13215537
7. Palsgrove DN, Taheri D, Springer SU et al (2019) Targeted sequencing of plasmacytoid urothelial carcinoma reveals frequent TERT promoter
mutations. Hum Pathol, 85, 1-9. doi:10.1016/j.humpath.2018.10.033
8. Mathai RA, Vidya RVS, Reddy BS et al (2019) Potential Utility of Liquid Biopsy as a Diagnostic and Prognostic Tool for the Assessment of Solid
Tumors: Implications in the Precision OncologyClin Med, 8(3). doi:10.3390/jcm8030373
9. Siraj AK, Bu R, Iqbal K et al (2020) Telomerase reverse transcriptase promoter mutations in cancers derived from multiple organ sites among
middle eastern population. Genomics, 112(2), 1746-1753. doi:10.1016/j.ygeno.2019.09.017
10. Alharbi RA (2020) Proteomics approach and techniques in identification of reliable biomarkers for diseases. Saudi Biol Sci, 27(3), 968-974.
doi:10.1016/j.sjbs.2020.01.020
11. Aslam B, Basit M, Nisar MA et al (2017) Proteomics: Technologies and Their Applications. Chromatogr Sci, 55(2), 182-196.
doi:10.1093/chromsci/bmw167
12. Gaston KE, and Grossman HB (2010) Proteomic assays for the detection of urothelial cancer. Methods Mol Biol, 641, 303-323. doi:10.1007/978-1-60761-711-2_17
13. Shirodkar SP, and Lokeshwar VB (2009) Potential new urinary markers in the early detection of bladder cancer. Curr Opin Urol, 19(5), 488-493. doi:10.1097/MOU.0b013e32832eb3a0
14. Veyssiere H, Bidet Y, Penault-Llorca F et al (2022) Circulating proteins as predictive and prognostic biomarkers in breast cancer. Clin
Proteomics, 19(1), 25. doi:10.1186/s12014-022-09362-0
15. Wang J, Zhao X, Jiang XL et al (2022) Diagnostic performance of nuclear matrix protein 22 and urine cytology for bladder cancer: A meta-analysis. Diagn Cytopathol, 50(6), 300-312. doi:10.1002/dc.24954
16. Mati Q, Qamar S, Ashraf S et al (2020) Tissue Nuclear Matrix Protein Expression 22 in Various Grades and Stages of Bladder Cancer. Coll
Physicians Surg Pak, 30(12), 1321-1325. doi:10.29271/jcpsp.2020.12.1321
17. Lopez-Bergami P, and Barbero G (2020) The emerging role of Wnt5a in the promotion of a proinflammatory and immunosuppressive tumor microenvironment. Cancer Metastasis Rev, 39(3), 933-952. doi:10.1007/s10555-020-09878-7
18. Wu GJ, Bao JS, Yue ZJ, et al (2018) Elevated expression of matrix metalloproteinase-9 is associated with bladder cancer pathogenesis.
Cancer Res Ther, 14(Supplement), S54-S59. doi:10.4103/0973-1482.163761
19. Sanchez-Martin V, Jimenez-Garcia L, Herranz S et al (2019) alpha-Hispanolol Induces Apoptosis and Suppresses Migration and Invasion of
Glioblastoma Cells Likely via Downregulation of MMP-2/9 Expression and p38MAPK Attenuation. Front Pharmacol, 10, 935.
doi:10.3389/fphar.2019.00935
20. Papanicolaou GN, and Marshall VF (1945) Urine Sediment Smears as a Diagnostic Procedure in Cancers of the Urinary Tract. Science, 101(2629), 519-520. doi:10.1126/science.101.2629.519
21. Barkan GA, Wojcik EM, Nayar R et al (2016) The Paris System for Reporting Urinary Cytology: The Quest to Develop a Standardized Terminology. Acta Cytol, 60(3), 185-197. doi:10.1159/000446270
22. Venu C, Joseph LC, Jonathan II (2009) Histologic variants of urothelial bladder cancer and nonurothelial histology in bladder cancer. Can
Urol Assoc 3: S193–S198. doi: 10.5489/cuaj.1195
23. Antoni S, Ferlay J, Soerjomataram I et al (2017) Bladder Cancer Incidence and Mortality: A Global Overview and Recent Trends. Eur Urol, 71(1), 96-108. doi:10.1016/j.eururo.2016.06.010
24. Hosen MI, Sheikh M, Zvereva M et al (2020) Urinary TERT promoter mutations are detectable up to 10 years prior to clinical diagnosis of bladder cancer: Evidence from the Golestan Cohort Study. EBioMedicine, 53, 102643.
doi:10.1016/j.ebiom.2020.102643
25. Chiba K, Lorbeer FK, Shain AH et al (2017) Mutations in the promoter of the telomerase gene TERT contribute to tumorigenesis by a two-step mechanism. Science, 357(6358), 1416-1420. doi:10.1126/science.aao0535
26. Bialek L, Bilski K, Dobruch J et al (2022) NonInvasive Biomarkers in the Diagnosis of Upper Urinary Tract Urothelial Carcinoma-A Systematic Review. Cancers (Basel), 14(6). doi:10.3390/cancers14061520
27. Wang K, Liu T, Ge N et al (2014) TERT promoter mutations are associated with distant metastases in upper tract urothelial carcinomas and serve as urinary biomarkers detected by a sensitive castPCR. Oncotarget, 5(23), 12428-12439. doi:10.18632/oncotarget.2660
28. Pakmanesh H, Anvari O, Forey N et al (2022) TERT Promoter Mutations as Simple and NonInvasive Urinary Biomarkers for the Detection of Urothelial Bladder Cancer in a High-Risk Region. Int Mol Sci, 23(22). doi:10.3390/ijms232214319
29. Tilki D, Burger M, Dalbagni G et al (2011) Urine markers for detection and surveillance of nonmuscle-invasive bladder cancer. Eur Urol, 60(3), 484-492. doi:10.1016/j.eururo.2011.05.053
30. Chan E, Balassanian R, Tabatabai ZL et al (2018) Improved diagnostic precision of urine cytology by implementation of The Paris System and the use of cell blocks. Cancer Cytopathol, 126(9), 809-816. doi:10.1002/cncy.22034
31. Al-Delaimy WK, Awadalla A, El-Assmy A et al (2022) Comparison of urinary telomerase, CD44, and NMP22 assays for detection of bladder squamous cell carcinoma. Curr Urol, 16(3), 154-159. doi:10.1097/CU9.0000000000000098
32. Yang HJ, Liu T, and Xiong Y (2022) Anti-cancer effect of LINC00478 in bladder cancer correlates with KDM1A-dependent MMP9 demethylation. Cell Death Discov, 8(1), 242. doi:10.1038/s41420-022-00956-z
33. Batista R, Lima L, Vinagre J et al (2020) TERT Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer
Patients. Int Mol Sci, 21(3). doi:10.3390/ijms21030947
34. Hayashi Y, Fujita K, Nojima S et al (2020) TERT C228T mutation in non-malignant bladder urothelium is associated with intravesical
recurrence for patients with non-muscle invasive bladder cancer. Mol Oncol, 14(10), 2375-2383. doi:10.1002/1878-0261.12746
35. Hayashi Y, Fujita K, Netto GJ, et al (2021) Clinical Application of TERT Promoter Mutationsin Urothelial Carcinoma. Front Oncol, 11, 705440.
doi:10.3389/fonc.2021.705440
36. Wu S, Huang P, Li C et al (2014) Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study. Eur Urol, 65(2), 274-277. doi:10.1016/j.eururo.2013.10.038
37. Biswas, S. ., Bhagyasree, V. ., & Rathod, V. N. . (2022). A CHECKLIST OF BIRDS AND DIVERSITY OF AVIAN FAUNA IN
MUDASARLOVA RESERVOIR OF VISAKHAPATNAM, INDIA . Journal Of Advanced Zoology, 42(02), 165–175. https://doi.org/10.17762/jaz.v42i02.51
38. Faisal, H. T. ., Abid, M. K. ., & Abed, A. . (2022). Study Of Some Biochemical Parameters in Dose During Pregnancy in Goats. Journal Of Advanced Zoology, 43(1), 01–06. https://doi.org/10.17762/jaz.v43i1.109
39. Wankhade, L. N. . (2022). STUDY ON BUTTERFLY FAUNA OF KARANJA (GHADGE) TAHSIL OF DISTRICT WARDHA
(MAHARASHTRA). Journal Of Advanced Zoology, 42(02), 186–193. https://doi.org/10.17762/jaz.v42i02.53
40. Descotes F, Kara N, Decaussin-Petrucci M et al (2017) Non-invasive prediction of recurrence in bladder cancer by detecting somatic TERT
promoter mutations in urine. Br J Cancer, 117(4), 583-587. doi:10.1038/bjc.2017.210
41. Rachakonda PS, Hosen I, de Verdier PJ et al (2013) TERT promoter mutations in bladder cancer affect patient survival and disease
recurrence through modification by a common polymorphism. Proc Natl Acad Sci U S A, 110(43), 17426-17431. doi:10.1073/pnas.1310522110
42. de Kouchkovsky I, Zhang L, Philip EJ et al (2021) TERT promoter mutations and other prognostic factors in patients with advanced urothelial carcinoma treated with an immune checkpoint inhibitor. Immunother Cancer, 9(5). doi:10.1136/jitc-2020-002127
43. Faisal, H. T. ., Abid, M. K. ., & Abed, A. . (2022). Study Of Some Biochemical Parameters in Dose During Pregnancy in Goats. Journal Of Advanced Zoology, 43(1), 01–06. https://doi.org/10.17762/jaz.v43i1.109
44. Gulati, H. ., & Rana, S. . (2022). Habitat Preference and Current Threats to The Sarus Cranes Grus Antigone (Aves: Gruiformes:
Gruidae) In Important Bird Areas of Haryana, India: Implications for Determining Effective Conservation Actions. Journal Of Advanced
Zoology, 43(1), 07–16. Retrieved from http://jazindia.com/index.php/jaz/article/view/110
45. Mokhtar, A. R. R. A. S. . (2022). Development Of Saponin Based Wettable Powder Formulation from Phaleria macrocarpa To Control Pomacea maculate. Journal Of Advanced Zoology, 43(1), 17–31. Retrieved from http://jazindia.com/index.php/jaz/article/view/111
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Mar 26, 2023
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Samah Mamdouh, Gehan Hammad, Tarek Aboushousha, Gehan Safwat, & Khaled Elesaily. (2023). Diagnostic Performances of Urine Cytology and TERT Promoter Mutations in Bladder Cancer. Journal of Population Therapeutics and Clinical Pharmacology, 30(4), 68–83. https://doi.org/10.47750/jptcp.2023.30.04.008
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