Markers for Early Diagnosis and Post-operative Recurrence Monitoring of Bladder Cancer
The diagnosis and management of bladder cancer (BC) are high complex due to cancer heterogeneity among patients. Thus, biomarkers play pivotal roles in the diagnosis, prognosis determination, and planning of therapeutic intervention of BC. With years of research and discovery, many candidate markers for BC have emerged. The alterations of nucleosides, proteins, post-translational modifications, and cells are the candidate markers for early diagnosis and post-operative recurrence monitoring of BC. This review mainly discusses the recent progresses in the proteins and nucleosides markers for diagnosis and recurrence monitoring of BC. In the detection of BC, some potential nucleoside-based markers have been reported, including telomerase reverse transcriptase (TERT) gene, microsatellite, and chromosome instability, whereas the protein markers include bladder tumor antigen, nuclear matrix protein family (Nuclear matrix protein 22), fibrin/fibrin degradation product, and aberrantly glycosylated integrin α3β1. Besides, the performance of diagnostic methods based on these markers are reviewed. The sensitivity and specificity of candidate markers and detection methods of BC are compared. In summary, this review provides invaluable information about the early diagnosis and recurrence of BC, which guides the development and improvement of novel markers for early diagnosis and post-operative recurrence monitoring of BC in future.
Leal J, Luengo-Fernandez R, Sullivan R, et al., 2016, Economic Burden of Bladder Cancer Across the European Union. Eur Urol, 69:438–47. DOI: 10.1016/j.eururo.2015.10.024.
Bray F, Ferlay J, Soerjomataram I, et al., 2018, Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin, 68:394–424. DOI: 10.3322/caac.21609.
Britton JP, Dowell AC, Whelan P, et al, 1989, Dipstick Haematuria and Bladder Cancer in Men Over 60: Results of a Community Study. BMJ, 299:1010–2. DOI: 10.1136/bmj.299.6706.1010.
Budman LI, Kassouf W, Steinberg JR, 2008, Biomarkers for Detection and Surveillance of Bladder Cancer. Can Urol Assoc J, 2:212–21.
Zhu CZ, Ting HN, Ng KH, et al., 2019, A Review on the Accuracy of Bladder Cancer Detection Methods. J Cancer, 10:4038–44. DOI: 10.7150/jca.28989.
Soubra A, Risk MC, 2015, Diagnostics Techniques in Nonmuscle Invasive Bladder Cancer. Indian J Urol, 31:283–8. DOI: 10.4103/0970-1591.166449.
Garczyk S, Ortiz-Brüchle N, Schneider U, et al., 2020, Next-generation Sequencing Reveals Potential Predictive Biomarkers and Targets of Therapy for Urothelial Carcinoma in Situ of the Urinary Bladder. Am J Pathol, 190:323–32. DOI: 10.1016/j.ajpath.2019.10.004.
Costello JC, Theodorescu D, 2014, Decade in Review-bladder Cancer: International Progress: From Cytology to Genomics. Nat Rev Urol, 11:609–10. DOI: 10.1038/nrurol.2014.236.
Kim NW, Piatyszek MA, Prowse KR, et al., 1994, Specific Association of Human Telomerase Activity with Immortal Cells and Cancer. Science, 266:2011–5.
Nair SK, Heiser A, Boczkowski D, et al., 2000, Induction of Cytotoxic T Cell Responses and Tumor Immunity Against Unrelated Tumors Using Telomerase Reverse Transcriptase RNA Transfected Dendritic Cells. Nat Med, 6:1011–7. DOI: 10.1038/79519.
Schmetter BS, Habicht KK, Lamm DL, et al., 1997, A Multicenter Trial Evaluation of the Fibrin/Fibrinogen Degradation Products Test for Detection and Monitoring of Bladder Cancer. J Urol, 158:801–5. DOI: 10.1016/s0022-5347(01)64321-0.
Horn S, Figl A, Rachakonda PS, et al., 2013, TERT Promoter Mutations in Familial and Sporadic Melanoma. Science, 339:959–61.
Huang FW, Hodis E, Xu MJ, et al., 2013, Highly Recurrent TERT Promoter Mutations in Human Melanoma. Science, 339:957–9. DOI: 10.1126/science.1229259.
Killela PJ, Reitman ZJ, Jiao Y, et al., 2013, TERT Promoter Mutations Occur Frequently in Gliomas and a Subset of Tumors Derived from Cells with Low Rates of Self-renewal. Proc Natl Acad Sci U S A, 110:6021–6. DOI: 10.3410/f.718015949.793477772.
Liu X, Bishop J, Shan Y, et al., 2013, Highly Prevalent TERT Promoter Mutations in Aggressive Thyroid Cancers. Endocr Relat Cancer, 20:603–10.
Nault JC, Mallet M, Pilati C, et al., 2013, High Frequency of Telomerase Reverse-transcriptase Promoter Somatic Mutations in Hepatocellular Carcinoma and Preneoplastic Lesions. Nat Commun, 4:2218. DOI: 10.1038/ncomms3577.
Vinagre J, Almeida A, Pópulo H, et al., 2013, Frequency of TERT Promoter Mutations in Human Cancers. Nat Commun, 4:2185.
Vinagre J, Pinto V, Celestino R, et al., 2014, Telomerase Promoter Mutations in Cancer: An Emerging Molecular Biomarker? Virchows Arch, 465:119–33.
Borah S, Xi L, Zaug AJ, et al., 2015, TERT Promoter Mutations and Telomerase Reactivation in Urothelial Cancer. Science, 347:1006–10.
Kim WJ, Kim EJ, Kim SK, et al., 2010, Predictive Value of Progression-related Gene Classifier in Primary Non-muscle Invasive Bladder Cancer. Mol Cancer, 9:3. DOI: 10.1186/1476-4598-9-3.
Sanchez-Carbayo M, Socci ND, Lozano J, et al., 2006, Defining Molecular Profiles of Poor Outcome in Patients with Invasive Bladder Cancer Using Oligonucleotide Microarrays. J Clin Oncol, 24:778–89. DOI: 10.1200/jco.2005.03.2375.
Di Meo A, Bartlett J, Cheng Y, et al., 2017, Liquid Biopsy: A Step Forward Towards Precision Medicine in Urologic Malignancies. Mol Cancer, 16:80. DOI: 10.1186/s12943-017-0644-5.
Wang K, Liu T, Liu C, et al., 2015, TERT Promoter Mutations and TERT mRNA But Not FGFR3 Mutations are Urinary Biomarkers in Han Chinese Patients with Urothelial Bladder Cancer. Oncologist, 20:263–9. DOI: 10.1634/theoncologist.2014-0391.
Stasik S, Salomo K, Heberling U, et al., 2019, Evaluation of TERT Promoter Mutations in Urinary Cell-free DNA and Sediment DNA for Detection of Bladder Cancer. Clin Biochem, 64:60–3. DOI: 10.1016/j.clinbiochem.2018.11.009.
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.
Kurtis B, Zhuge J, Ojaimi C, et al., 2016, Recurrent TERT Promoter Mutations in Urothelial Carcinoma and Potential Clinical Applications. Ann Diagn Pathol, 21:7–11.
Mao L, Schoenberg MP, Scicchitano M, et al., 1996, Molecular Detection of Primary Bladder Cancer by Microsatellite Analysis. Science, 271:659–62. DOI: 10.1126/science.271.5249.659.
Legrand G, Soliman H, Dubosq F, et al., 2011, Prevalence and Spectrum of Microsatellite Alterations in Nonmuscle Invasive Bladder Cancers. Am J Cancer Res, 1:595–603.
van Tilborg AA, Kompier LC, Lurkin I, et al., 2012, Selection of Microsatellite Markers for Bladder Cancer Diagnosis Without the Need for Corresponding Blood. PLoS One, 7:e43345. DOI: 10.1371/journal.pone.0043345.
30 Asali MG, Kaneti J, Manor E, 2007, Numerical Aberrations of Chromosomes 11 and 17 Detected by Fish-Fluorescence in Situ Hybridization Combined with Cytology in Exfoliated Cells from Voided Urine in Patients with Urothelial Carcinoma of the Bladder. Harefuah, 146:914–9.
Cairns P, Shaw ME, Knowles MA, 1993, Initiation of Bladder Cancer May Involve Deletion of a Tumour-suppressor Gene on Chromosome 9. Oncogene, 8:1083–5.
Yurakh AO, Ramos D, Calabuig-Fariñas S, et al., 2006, Molecular and Immunohistochemical Analysis of the Prognostic Value of Cell-cycle Regulators in Urothelial Neoplasms of the Bladder. Eur Urol, 50:506–15. DOI: 10.1016/j.eururo.2006.03.027.
Petrov SV, Malkhasyan KA, Ulyanin MY, et al., 2012, The Value of the Preoperative FISH Test in Unscreened Bladder Cancer Patients with TUR Indications. Pathol Oncol Res, 18:1059–66. DOI: 10.1007/s12253-012-9544-6.
Dimashkieh H, Wolff DJ, Smith TM, et al., 2013, Evaluation of Urovysion and Cytology for Bladder Cancer Detection: A Study of 1835 Paired Urine Samples with Clinical and Histologic Correlation. Cancer Cytopathol, 121:591–7. DOI: 10.1002/cncy.21327.
Boman H, Hedelin H, Holmang S, 2002, Four Bladder Tumor Markers Have a Disappointingly Low Sensitivity for Small Size and Low Grade Recurrence. J Urol, 167:80–3. DOI: 10.1016/s0022-5347(05)65387-6.
Miyake M, Goodison S, Rizwani W, et al., 2012, Urinary BTA: Indicator of Bladder Cancer or of Hematuria. World J Urol, 30:869–73. DOI: 10.1007/s00345-012-0935-9-9.
Krabbe LM, Woldu SL, Shariat SF, et al., 2016, Improving Diagnostic Molecular Tests to Monitor Urothelial Carcinoma Recurrence. Expert Rev Mol Diagn, 16:1189–99. DOI: 10.1080/14737159.2016.1244006.
Balci M, Tuncel A, Guzel O, et al., 2015, Use of the Nuclear Matrix Protein 22 Bladder Chek Test in the Diagnosis of Residual Urothelial Cancer Before a Second Transurethral Resection of Bladder Cancer. Int Urol Nephrol, 47:473–7. DOI: 10.1007/s11255-015-0921-4.
Hosseini J, Golshan AR, Mazloomfard MM, et al., 2012, Detection of Recurrent Bladder Cancer: NMP22 Test or Urine Cytology? Urol J, 9:367–72.
Luyendyk JP, Schoenecker JG, Flick MJ, 2019, The Multifaceted Role of Fibrinogen in Tissue Injury and Inflammation. Blood, 133:511–20. DOI: 10.1182/blood-2018-07-818211.
Tsihlias J, Grossman HB, 2000, The Utility of Fibrin/Fibrinogen Degradation Products in Superficial Bladder Cancer. Urol Clin North Am, 27:39–46. DOI: 10.1016/s0094-0143(05)70232-9.
John A, Gorzelanny C, Bauer AT, et al., 2017, Role of the Coagulation System in Genitourinary Cancers: Review. Clin Genitourin Cancer, 16:E29–37. DOI: 10.1016/j.clgc.2017.07.013.
Siemens DR, Morales A, Johnston B, et al., 2003, A Comparative Analysis of Rapid Urine Tests for the Diagnosis of Upper Urinary Tract Malignancy. Can J Urol, 10:1754–8.
Pirtskalaishvili G, Konety BR, Getzenberg RH, 1999, Update on Urine-based Markers for Bladder Cancer. How Sensitive and Specific are the New Noninvasive Tests? Postgrad Med, 106:85–6. DOI: 10.3810/pgm.1999.11.774.
Topsakal M, Karadeniz T, Anac M, et al., 2001, Assessment of Fibrin-fibrinogen Degradation Products (Accu-Dx) Test in Bladder Cancer Patients. Eur Urol, 39:287–91. DOI: 10.1159/000052455.
Li C, Yang Z, Du Y, et al., 2014, BCMab1, a Monoclonal Antibody Against Aberrantly Glycosylated Integrin Alpha3beta1, Has Potent Antitumor Activity of Bladder Cancer in Vivo. Clin Cancer Res, 20:4001–13. DOI: 10.1158/1078-0432.ccr-13-3397.
Lokeshwar VB, Obek C, Pham HT, et al., 2000, Urinary Hyaluronic Acid and Hyaluronidase: Markers for Bladder Cancer Detection and Evaluation of Grade. J Urol, 163:348–56. DOI: 10.1016/s0022-5347(05)68050-0.
Pode D, Golijanin D, Sherman Y, et al., 1998, Immunostaining of Lewis X in Cells from Voided Urine, Cytopathology and Ultrasound for Noninvasive Detection of Bladder Tumors. J Urol, 159:389–92. DOI: 10.1016/s0022-5347(01)63928-4.
Chen D, Xu J, Zhang Q, 2018, Detection of Survivin Expression in Bladder Cancer and Renal Cell Carcinoma Using Specific Monoclonal Antibodies. Oncol Rep, 39:2817–28. DOI: 10.3892/or.2018.6359.
Wang ZY, Li HY, Wang H, et al., 2018, Bladder Cancer-specific Nuclear Matrix Proteins-4 May Be a Potential Biomarker for Non-muscle-invasive Bladder Cancer Detection. Dis Markers, 2018:5609395. DOI: 10.1155/2019/6432596.
Lai Y, Ye J, Chen J, et al., 2010, UPK3A: A Promising Novel Urinary Marker for the Detection of Bladder Cancer. Urology, 76:514, e6–11. DOI: 10.1016/j.urology.2009.11.045.
Jiang J, Ulbright TM, Younger C, et al., 2001, Cytokeratin 7 and Cytokeratin 20 in Primary Urinary Bladder Carcinoma and Matched Lymph Node Metastasis. Arch Pathol Lab Med, 125:921–3.
53 van Rhijn BW, van der Poel HG, Boon ME, et al., 2000, Presence of Carcinoma in Situ and High 2C-deviation Index are the Best Predictors of Invasive Transitional Cell Carcinoma of the Bladder in Patients with High-risk Quanticyt. Urology, 55:363–7. DOI: 10.1016/s0090-4295(99)00460-4.
Feil G, Zumbrägel A, Päulgen-Nelde HJ, et al., 2003, Accuracy of the ImmunoCyt Assay in the Diagnosis of Transitional Cell Carcinoma of the Urinary Bladder. Anticancer Res, 23:963–7.
Sarosdy MF, Hudson MA, Ellis WJ, et al., 1997, Improved Detection of Recurrent Bladder Cancer Using the Bard BTA Stat Test. Urology, 50:349–53.
Saad A, Hanbury DC, McNicholas TA, et al., 2002, A Study Comparing Various Noninvasive Methods of Detecting Bladder Cancer in Urine. BJU Int, 89:369–73. DOI: 10.1046/j.1464-4096.2001.01699.x.
Li HX, Wang MR, Zhao H, et al., 2013, Comparison of Fluorescence in Situ Hybridization, NMP22 Bladderchek, and Urinary Liquid-based Cytology in the Detection of Bladder Urothelial Carcinoma. Diagn Cytopathol, 41:852–7. DOI: 10.1002/dc.22969.