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Research Progress of Urine Biomarkers in the Diagnosis, Treatment, and Prognosis of Bladder Cancer

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Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 1306))

Abstract

Bladder cancer (BC) is one of the most common tumor with high incidence. Relative to other cancers, BC has a high rate of recurrence, which results in increased mortality. As a result, early diagnosis and life-long monitoring are clinically significant for improving the long-term survival rate of BC patients. At present, the main methods of BC detection are cystoscopy and biopsy; however, these procedures can be invasive and expensive. This can lead to patient refusal and reluctance for monitoring. There are several BC biomarkers that have been approved by the FDA, but their sensitivity, specificity, and diagnostic accuracy are not ideal. More research is needed to identify suitable biomarkers that can be used for early detection, evaluation, and observation. There has been heavy research in the proteomics and genomics of BC and many potential biomarkers have been found. Although the advent of metabonomics came late, with the recent development of advanced analytical technology and bioinformatics, metabonomics has become a widely used diagnostic tool in clinical and biomedical research. It should be emphasized that despite progress in new biomarkers for BC diagnosis, there remains challenges and limitations in metabonomics research that affects its translation into clinical practice. In this chapter, the latest literature on BC biomarkers was reviewed.

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References

  1. Siegel, R.L., Miller, K.D., Jemal, A.: Cancer statistics, 2019. CA Cancer J. Clin. 69, 7–34 (2019)

    Article  PubMed  Google Scholar 

  2. Mitra, A.P., Cote, R.J.: Molecular pathogenesis and diagnostics of bladder cancer. Annu. Rev. Pathol. 4, 251–285 (2009)

    Article  CAS  PubMed  Google Scholar 

  3. Ruder, A.M., Fine, L.J., Sundin, D.S.: National estimates of occupational exposure to animal bladder tumorigens. J. Occup. Med. 32, 797–805 (1990)

    Article  CAS  PubMed  Google Scholar 

  4. Pelucchi, C., Bosetti, C., Negri, E., Malvezzi, M., La Vecchia, C.: Mechanisms of disease: the epidemiology of bladder cancer. Nat. Clin. Pract. Urol. 3, 327–340 (2006)

    Article  CAS  PubMed  Google Scholar 

  5. Castelao, J.E., Yuan, J.M., Gago-Dominguez, M., Yu, M.C., Ross, R.K.: Non-steroidal anti-inflammatory drugs and bladder cancer prevention. Br. J. Cancer. 82, 1364–1369 (2000)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Lokeshwar, V.B., Habuchi, T., Grossman, H.B., Murphy, W.M., Hautmann, S.H., Hemstreet 3rd, G.P., Bono, A.V., Getzenberg, R.H., Goebell, P., Schmitz-Drager, B.J., et al.: Bladder tumor markers beyond cytology: international consensus panel on bladder tumor markers. Urology. 66, 35–63 (2005)

    Article  PubMed  Google Scholar 

  7. Sloan, F.A., Yashkin, A.P., Akushevich, I., Inman, B.A.: The cost to medicare of bladder cancer care. Eur Urol Oncol. 3, 515–522 (2019)

    Article  PubMed  Google Scholar 

  8. James, A.C., Gore, J.L.: The costs of non-muscle invasive bladder cancer. Urol. Clin. North Am. 40, 261–269 (2013)

    Article  PubMed  Google Scholar 

  9. Moch, H., Cubilla, A.L., Humphrey, P.A., Reuter, V.E., Ulbright, T.M.: The 2016 WHO classification of tumours of the urinary system and male genital organs-part a: renal, penile, and testicular tumours. Eur. Urol. 70, 93–105 (2016)

    Article  PubMed  Google Scholar 

  10. Eich, M.L., Dyrskjot, L., Netto, G.J.: Toward personalized management in bladder cancer: the promise of novel molecular taxonomy. Virchows Arch. 471, 271–280 (2017)

    Article  PubMed  Google Scholar 

  11. Kirkali, Z., Chan, T., Manoharan, M., Algaba, F., Busch, C., Cheng, L., Kiemeney, L., Kriegmair, M., Montironi, R., Murphy, W.M., et al.: Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology. 66, 4–34 (2005)

    Article  PubMed  Google Scholar 

  12. Wang, G., McKenney, J.K.: Urinary bladder pathology: World Health Organization classification and American joint committee on cancer staging update. Arch. Pathol. Lab. Med. 143, 571–577 (2019)

    Article  CAS  PubMed  Google Scholar 

  13. Reuter, V.E.: The pathology of bladder cancer. Urology. 67, 11–17 (2006) discussion 17–18

    Google Scholar 

  14. Damrauer, J.S., Hoadley, K.A., Chism, D.D., Fan, C., Tiganelli, C.J., Wobker, S.E., Yeh, J.J., Milowsky, M.I., Iyer, G., Parker, J.S., et al.: Intrinsic subtypes of high-grade bladder cancer reflect the hallmarks of breast cancer biology. Proc. Natl. Acad. Sci. U. S. A. 111, 3110–3115 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Choi, W., Porten, S., Kim, S., Willis, D., Plimack, E.R., Hoffman-Censits, J., Roth, B., Cheng, T., Tran, M., Lee, I.L., et al.: Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy. Cancer Cell. 25, 152–165 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cancer Genome Atlas Research, N.: Comprehensive molecular characterization of urothelial bladder carcinoma. Nature. 507, 315–322 (2014)

    Article  CAS  Google Scholar 

  17. Sjodahl, G., Lauss, M., Lovgren, K., Chebil, G., Gudjonsson, S., Veerla, S., Patschan, O., Aine, M., Ferno, M., Ringner, M., et al.: A molecular taxonomy for urothelial carcinoma. Clin. Cancer Res. 18, 3377–3386 (2012)

    Article  PubMed  CAS  Google Scholar 

  18. Kim, J., Akbani, R., Creighton, C.J., Lerner, S.P., Weinstein, J.N., Getz, G., Kwiatkowski, D.J.: Invasive bladder cancer: genomic insights and therapeutic promise. Clin. Cancer Res. 21, 4514–4524 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Sjodahl, G., Eriksson, P., Liedberg, F., Hoglund, M.: Molecular classification of urothelial carcinoma: global mRNA classification versus tumour-cell phenotype classification. J. Pathol. 242, 113–125 (2017)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Kardos, J., Chai, S., Mose, L.E., Selitsky, S.R., Krishnan, B., Saito, R., Iglesia, M.D., Milowsky, M.I., Parker, J.S., Kim, W.Y., et al.: Claudin-low bladder tumors are immune infiltrated and actively immune suppressed. JCI Insight. 1, e85902 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hurle, R., Losa, A., Manzetti, A., Lembo, A.: Upper urinary tract tumors developing after treatment of superficial bladder cancer: 7-year follow-up of 591 consecutive patients. Urology. 53, 1144–1148 (1999)

    Article  CAS  PubMed  Google Scholar 

  22. Lotan, Y., Svatek, R.S., Sagalowsky, A.I.: Should we screen for bladder cancer in a high-risk population?: a cost per life-year saved analysis. Cancer. 107, 982–990 (2006)

    Article  PubMed  Google Scholar 

  23. Daneshmand, S., Bazargani, S.T., Bivalacqua, T.J., Holzbeierlein, J.M., Willard, B., Taylor, J.M., Liao, J.C., Pohar, K., Tierney, J., Konety, B., et al.: Blue light cystoscopy for the diagnosis of bladder cancer: results from the US prospective multicenter registry. Urol Oncol. 36, 361.e1–361.e6 (2018)

    Article  Google Scholar 

  24. de Martino, M., Shariat, S.F., Hofbauer, S.L., Lucca, I., Taus, C., Wiener, H.G., Haitel, A., Susani, M., Klatte, T.: Aurora A kinase as a diagnostic urinary marker for urothelial bladder cancer. World J. Urol. 33, 105–110 (2015)

    Article  PubMed  CAS  Google Scholar 

  25. Arnold Egloff, S.A., Du, L., Loomans, H.A., Starchenko, A., Su, P.F., Ketova, T., Knoll, P.B., Wang, J., Haddad, A.Q., Fadare, O., et al.: Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer. Oncotarget. 8, 722–741 (2017)

    Article  PubMed  Google Scholar 

  26. Pozzi, V., Di Ruscio, G., Sartini, D., Campagna, R., Seta, R., Fulvi, P., Vici, A., Milanese, G., Brandoni, G., Galosi, A.B., et al.: Clinical performance and utility of a NNMT-based urine test for bladder cancer. Int. J. Biol. Markers. 33, 94–101 (2018)

    Article  CAS  PubMed  Google Scholar 

  27. Choi, S., Shin, J.H., Lee, Y.R., Joo, H.K., Song, K.H., Na, Y.G., Chang, S.J., Lim, J.S., Jeon, B.H.: Urinary APE1/Ref-1: a potential bladder cancer biomarker. Dis. Markers. 2016, 7276502 (2016)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Mi, Y., Zhao, Y., Shi, F., Zhang, M., Wang, C., Liu, X.: Diagnostic accuracy of urine cytokeratin 20 for bladder cancer: a meta-analysis. Asia Pac. J. Clin. Oncol. 15, e11–e19 (2019)

    Article  PubMed  Google Scholar 

  29. Ecke, T.H., Weiss, S., Stephan, C., Hallmann, S., Barski, D., Otto, T., Gerullis, H.: UBC((R)) rapid test for detection of carcinoma in situ for bladder cancer. Tumour Biol. 39, 1010428317701624 (2017)

    Article  PubMed  CAS  Google Scholar 

  30. Chen, Y.T., Chen, C.L., Chen, H.W., Chung, T., Wu, C.C., Chen, C.D., Hsu, C.W., Chen, M.C., Tsui, K.H., Chang, P.L., et al.: Discovery of novel bladder cancer biomarkers by comparative urine proteomics using iTRAQ technology. J. Proteome Res. 9, 5803–5815 (2010)

    Article  CAS  PubMed  Google Scholar 

  31. Chen, Y.T., Chen, H.W., Domanski, D., Smith, D.S., Liang, K.H., Wu, C.C., Chen, C.L., Chung, T., Chen, M.C., Chang, Y.S., et al.: Multiplexed quantification of 63 proteins in human urine by multiple reaction monitoring-based mass spectrometry for discovery of potential bladder cancer biomarkers. J. Proteome. 75, 3529–3545 (2012)

    Article  CAS  Google Scholar 

  32. Schiffer, E., Vlahou, A., Petrolekas, A., Stravodimos, K., Tauber, R., Geschwend, J.E., Neuhaus, J., Stolzenburg, J.U., Conaway, M.R., Mischak, H., et al.: Prediction of muscle-invasive bladder cancer using urinary proteomics. Clin. Cancer Res. 15, 4935–4943 (2009)

    Article  CAS  PubMed  Google Scholar 

  33. Masuda, N., Ogawa, O., Park, M., Liu, A.Y., Goodison, S., Dai, Y., Kozai, L., Furuya, H., Lotan, Y., Rosser, C.J., et al.: Meta-analysis of a 10-plex urine-based biomarker assay for the detection of bladder cancer. Oncotarget. 9, 7101–7111 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  34. Soukup, V., Kalousova, M., Capoun, O., Sobotka, R., Breyl, Z., Pesl, M., Zima, T., Hanus, T.: Panel of urinary diagnostic markers for non-invasive detection of primary and recurrent urothelial urinary bladder carcinoma. Urol. Int. 95, 56–64 (2015)

    Article  CAS  PubMed  Google Scholar 

  35. Shabayek, M.I., Sayed, O.M., Attaia, H.A., Awida, H.A., Abozeed, H.: Diagnostic evaluation of urinary angiogenin (ANG) and clusterin (CLU) as biomarker for bladder cancer. Pathol. Oncol. Res. 20, 859–866 (2014)

    Article  CAS  PubMed  Google Scholar 

  36. Salomo, K., Huebner, D., Boehme, M.U., Herr, A., Brabetz, W., Heberling, U., Hakenberg, O.W., Jahn, D., Grimm, M.O., Steinbach, D., et al.: Urinary transcript quantitation of CK20 and IGF2 for the non-invasive bladder cancer detection. J. Cancer Res. Clin. Oncol. 143, 1757–1769 (2017)

    Article  CAS  PubMed  Google Scholar 

  37. Snell, K.I.E., Ward, D.G., Gordon, N.S., Goldsmith, J.C., Sutton, A.J., Patel, P., James, N.D., Zeegers, M.P., Cheng, K.K., Bryan, R.T.: Exploring the roles of urinary HAI-1, EpCAM & EGFR in bladder cancer prognosis & risk stratification. Oncotarget. 9, 25244–25253 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  38. Yang, Y., Xu, J., Zhang, Q.: Detection of urinary survivin using a magnetic particles-based chemiluminescence immunoassay for the preliminary diagnosis of bladder cancer and renal cell carcinoma combined with LAPTM4B. Oncol. Lett. 15, 7923–7933 (2018)

    PubMed  PubMed Central  Google Scholar 

  39. Santi, R., Cai, T., Nobili, S., Galli, I.C., Amorosi, A., Comperat, E., Nesi, G.: Snail immunohistochemical overexpression correlates to recurrence risk in non-muscle invasive bladder cancer: results from a longitudinal cohort study. Virchows Arch. 472, 605–613 (2018)

    Article  CAS  PubMed  Google Scholar 

  40. Azevedo, R., Soares, J., Gaiteiro, C., Peixoto, A., Lima, L., Ferreira, D., Relvas-Santos, M., Fernandes, E., Tavares, A., Cotton, S., et al.: Glycan affinity magnetic nanoplatforms for urinary glycobiomarkers discovery in bladder cancer. Talanta. 184, 347–355 (2018)

    Article  CAS  PubMed  Google Scholar 

  41. Jin, X., Yun, S.J., Jeong, P., Kim, I.Y., Kim, W.J., Park, S.: Diagnosis of bladder cancer and prediction of survival by urinary metabolomics. Oncotarget. 5, 1635–1645 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  42. Zhou, Y., Song, R., Ma, C., Zhou, L., Liu, X., Yin, P., Zhang, Z., Sun, Y., Xu, C., Lu, X., et al.: Discovery and validation of potential urinary biomarkers for bladder cancer diagnosis using a pseudotargeted GC-MS metabolomics method. Oncotarget. 8, 20719–20728 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  43. Cheng, X., Liu, X., Liu, X., Guo, Z., Sun, H., Zhang, M., Ji, Z., Sun, W.: Metabolomics of non-muscle invasive bladder cancer: biomarkers for early detection of bladder cancer. Front. Oncol. 8, 494 (2018)

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tan, Y., Yin, P., Tang, L., Xing, W., Huang, Q., Cao, D., Zhao, X., Wang, W., Lu, X., Xu, Z., et al.: Metabolomics study of stepwise hepatocarcinogenesis from the model rats to patients: potential biomarkers effective for small hepatocellular carcinoma diagnosis. Mol. Cell. Proteomics. 11(M111), 010694 (2012)

    PubMed  Google Scholar 

  45. Yumba Mpanga, A., Siluk, D., Jacyna, J., Szerkus, O., Wawrzyniak, R., Markuszewski, M., Matuszewski, M., Kaliszan, R., Markuszewski, M.J.: Targeted metabolomics in bladder cancer: From analytical methods development and validation towards application to clinical samples. Anal. Chim. Acta. 1037, 188–199 (2018)

    Article  CAS  PubMed  Google Scholar 

  46. Shen, C., Sun, Z., Chen, D., Su, X., Jiang, J., Li, G., Lin, B., Yan, J.: Developing urinary metabolomic signatures as early bladder cancer diagnostic markers. OMICS. 19, 1–11 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Su, S.F., de Castro Abreu, A.L., Chihara, Y., Tsai, Y., Andreu-Vieyra, C., Daneshmand, S., Skinner, E.C., Jones, P.A., Siegmund, K.D., Liang, G.: A panel of three markers hyper- and hypomethylated in urine sediments accurately predicts bladder cancer recurrence. Clin. Cancer Res. 20, 1978–1989 (2014)

    Article  CAS  PubMed  Google Scholar 

  48. Pu, R.T., Laitala, L.E., Clark, D.P.: Methylation profiling of urothelial carcinoma in bladder biopsy and urine. Acta Cytol. 50, 499–506 (2006)

    Article  PubMed  Google Scholar 

  49. Hauser, S., Kogej, M., Fechner, G., Von Pezold, J., Vorreuther, R., Lummen, G., Muller, S.C., Ellinger, J.: Serum DNA hypermethylation in patients with bladder cancer: results of a prospective multicenter study. Anticancer Res. 33, 779–784 (2013)

    CAS  PubMed  Google Scholar 

  50. Renard, I., Joniau, S., van Cleynenbreugel, B., Collette, C., Naome, C., Vlassenbroeck, I., Nicolas, H., de Leval, J., Straub, J., Van Criekinge, W., et al.: Identification and validation of the methylated TWIST1 and NID2 genes through real-time methylation-specific polymerase chain reaction assays for the noninvasive detection of primary bladder cancer in urine samples. Eur. Urol. 58, 96–104 (2010)

    Article  CAS  PubMed  Google Scholar 

  51. Fantony, J.J., Longo, T.A., Gopalakrishna, A., Owusu, R., Lance, R.S., Foo, W.C., Inman, B.A., Abern, M.R.: Urinary NID2 and TWIST1 methylation to augment conventional urine cytology for the detection of bladder cancer. Cancer Biomark. 18, 381–387 (2017)

    Article  CAS  PubMed  Google Scholar 

  52. van der Heijden, A.G., Mengual, L., Ingelmo-Torres, M., Lozano, J.J., van Rijt-van de Westerlo, C.C.M., Baixauli, M., Geavlete, B., Moldoveanud, C., Ene, C., Dinney, C.P., et al.: Urine cell-based DNA methylation classifier for monitoring bladder cancer. Clin. Epigenetics. 10, 71 (2018)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Wang, Y., Yu, Y., Ye, R., Zhang, D., Li, Q., An, D., Fang, L., Lin, Y., Hou, Y., Xu, A., et al.: An epigenetic biomarker combination of PCDH17 and POU4F2 detects bladder cancer accurately by methylation analyses of urine sediment DNA in Han Chinese. Oncotarget. 7, 2754–2764 (2016)

    Article  PubMed  Google Scholar 

  54. Roperch, J.P., Grandchamp, B., Desgrandchamps, F., Mongiat-Artus, P., Ravery, V., Ouzaid, I., Roupret, M., Phe, V., Ciofu, C., Tubach, F., et al.: Promoter hypermethylation of HS3ST2, SEPTIN9 and SLIT2 combined with FGFR3 mutations as a sensitive/specific urinary assay for diagnosis and surveillance in patients with low or high-risk non-muscle-invasive bladder cancer. BMC Cancer. 16, 704 (2016)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Pietrusinski, M., Kepczynski, J.A., Borkowska, E., Traczyk-Borszynska, M., Constantinou, M., Kauzewski, B., Borowiec, M.: Detection of bladder cancer in urine sediments by a hypermethylation panel of selected tumor suppressor genes. Cancer Biomark. 18, 47–59 (2017)

    Article  CAS  PubMed  Google Scholar 

  56. Sasaki, H., Yoshiike, M., Nozawa, S., Usuba, W., Katsuoka, Y., Aida, K., Kitajima, K., Kudo, H., Hoshikawa, M., Yoshioka, Y., et al.: Expression level of urinary microRNA-146a-5p is increased in patients with bladder cancer and decreased in those after transurethral resection. Clin. Genitourin. Cancer. 14, e493–e499 (2016)

    Article  PubMed  Google Scholar 

  57. Hanke, M., Hoefig, K., Merz, H., Feller, A.C., Kausch, I., Jocham, D., Warnecke, J.M., Sczakiel, G.: A robust methodology to study urine microRNA as tumor marker: microRNA-126 and microRNA-182 are related to urinary bladder cancer. Urol. Oncol. 28, 655–661 (2010)

    Article  CAS  PubMed  Google Scholar 

  58. Wiklund, E.D., Gao, S., Hulf, T., Sibbritt, T., Nair, S., Costea, D.E., Villadsen, S.B., Bakholdt, V., Bramsen, J.B., Sorensen, J.A., et al.: MicroRNA alterations and associated aberrant DNA methylation patterns across multiple sample types in oral squamous cell carcinoma. PLoS One. 6, e27840 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Chen, Y.H., Wang, S.Q., Wu, X.L., Shen, M., Chen, Z.G., Chen, X.G., Liu, Y.X., Zhu, X.L., Guo, F., Duan, X.Z., et al.: Characterization of microRNAs expression profiling in one group of Chinese urothelial cell carcinoma identified by Solexa sequencing. Urol. Oncol. 31, 219–227 (2013)

    Article  CAS  PubMed  Google Scholar 

  60. Eissa, S., Matboli, M., Essawy, N.O., Kotb, Y.M.: Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis. Tumour Biol. 36, 9545–9552 (2015)

    Article  CAS  PubMed  Google Scholar 

  61. Pospisilova, S., Pazourkova, E., Horinek, A., Brisuda, A., Svobodova, I., Soukup, V., Hrbacek, J., Capoun, O., Hanus, T., Mares, J., et al.: MicroRNAs in urine supernatant as potential non-invasive markers for bladder cancer detection. Neoplasma. 63, 799–808 (2016)

    Article  CAS  PubMed  Google Scholar 

  62. Pignot, G., Cizeron-Clairac, G., Vacher, S., Susini, A., Tozlu, S., Vieillefond, A., Zerbib, M., Lidereau, R., Debre, B., Amsellem-Ouazana, D., et al.: microRNA expression profile in a large series of bladder tumors: identification of a 3-miRNA signature associated with aggressiveness of muscle-invasive bladder cancer. Int. J. Cancer. 132, 2479–2491 (2013)

    Article  CAS  PubMed  Google Scholar 

  63. Yun, S.J., Jeong, P., Kim, W.T., Kim, T.H., Lee, Y.S., Song, P.H., Choi, Y.H., Kim, I.Y., Moon, S.K., Kim, W.J.: Cell-free microRNAs in urine as diagnostic and prognostic biomarkers of bladder cancer. Int. J. Oncol. 41, 1871–1878 (2012)

    Article  CAS  PubMed  Google Scholar 

  64. Matsushita, R., Seki, N., Chiyomaru, T., Inoguchi, S., Ishihara, T., Goto, Y., Nishikawa, R., Mataki, H., Tatarano, S., Itesako, T., et al.: Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer. Br. J. Cancer. 113, 282–289 (2015)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Zhang, D.Z., Lau, K.M., Chan, E.S., Wang, G., Szeto, C.C., Wong, K., Choy, R.K., Ng, C.F.: Cell-free urinary microRNA-99a and microRNA-125b are diagnostic markers for the non-invasive screening of bladder cancer. PLoS One. 9, e100793 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Tolle, A., Jung, M., Rabenhorst, S., Kilic, E., Jung, K., Weikert, S.: Identification of microRNAs in blood and urine as tumour markers for the detection of urinary bladder cancer. Oncol. Rep. 30, 1949–1956 (2013)

    Article  PubMed  CAS  Google Scholar 

  67. Juracek, J., Peltanova, B., Dolezel, J., Fedorko, M., Pacik, D., Radova, L., Vesela, P., Svoboda, M., Slaby, O., Stanik, M.: Genome-wide identification of urinary cell-free microRNAs for non-invasive detection of bladder cancer. J. Cell. Mol. Med. 22, 2033–2038 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Bathe, O.F., Farshidfar, F.: From genotype to functional phenotype: unraveling the metabolomic features of colorectal cancer. Genes (Basel). 5, 536–560 (2014)

    Article  CAS  Google Scholar 

  69. Dinges, S.S., Hohm, A., Vandergrift, L.A., Nowak, J., Habbel, P., Kaltashov, I.A., Cheng, L.L.: Cancer metabolomic markers in urine: evidence, techniques and recommendations. Nat. Rev. Urol. 16, 339–362 (2019)

    Article  PubMed  Google Scholar 

  70. Roberts, L.D., Souza, A.L., Gerszten, R.E., Clish, C.B.: Targeted metabolomics. Curr Protoc Mol Biol. Chapter 30, Unit 30. 32, 31–24 (2012)

    Google Scholar 

  71. Alonso, A., Marsal, S., Julia, A.: Analytical methods in untargeted metabolomics: state of the art in 2015. Front. Bioeng. Biotechnol. 3, 23 (2015)

    Article  PubMed  PubMed Central  Google Scholar 

  72. Weiss, R.H., Kim, K.: Metabolomics in the study of kidney diseases. Nat. Rev. Nephrol. 8, 22–33 (2011)

    Article  PubMed  CAS  Google Scholar 

  73. Emwas, A.H.: The strengths and weaknesses of NMR spectroscopy and mass spectrometry with particular focus on metabolomics research. Methods Mol. Biol. 1277, 161–193 (2015)

    Article  CAS  PubMed  Google Scholar 

  74. Kalim, S., Rhee, E.P.: An overview of renal metabolomics. Kidney Int. 91, 61–69 (2017)

    Article  CAS  PubMed  Google Scholar 

  75. Griffin, J.L., Shockcor, J.P.: Metabolic profiles of cancer cells. Nat. Rev. Cancer. 4, 551–561 (2004)

    Article  CAS  PubMed  Google Scholar 

  76. Cheng, Y., Yang, X., Deng, X., Zhang, X., Li, P., Tao, J., Qin, C., Wei, J., Lu, Q.: Metabolomics in bladder cancer: a systematic review. Int. J. Clin. Exp. Med. 8, 11052–11063 (2015)

    PubMed  PubMed Central  Google Scholar 

  77. Assfalg, M., Bertini, I., Colangiuli, D., Luchinat, C., Schafer, H., Schutz, B., Spraul, M.: Evidence of different metabolic phenotypes in humans. Proc. Natl. Acad. Sci. U. S. A. 105, 1420–1424 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Lotan, Y., Shariat, S.F., Schmitz-Drager, B.J., Sanchez-Carbayo, M., Jankevicius, F., Racioppi, M., Minner, S.J., Stohr, B., Bassi, P.F., Grossman, H.B.: Considerations on implementing diagnostic markers into clinical decision making in bladder cancer. Urol. Oncol. 28, 441–448 (2010)

    Article  PubMed  Google Scholar 

  79. Barderas, M.G., Laborde, C.M., Posada, M., de la Cuesta, F., Zubiri, I., Vivanco, F., Alvarez-Llamas, G.: Metabolomic profiling for identification of novel potential biomarkers in cardiovascular diseases. J. Biomed. Biotechnol. 2011, 790132 (2011)

    Article  PubMed  PubMed Central  Google Scholar 

  80. Beckonert, O., Keun, H.C., Ebbels, T.M., Bundy, J., Holmes, E., Lindon, J.C., Nicholson, J.K.: Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat. Protoc. 2, 2692–2703 (2007)

    Article  CAS  PubMed  Google Scholar 

  81. Ellis, D.I., Dunn, W.B., Griffin, J.L., Allwood, J.W., Goodacre, R.: Metabolic fingerprinting as a diagnostic tool. Pharmacogenomics. 8, 1243–1266 (2007)

    Article  CAS  PubMed  Google Scholar 

  82. Mapelli, V., Olsson, L., Nielsen, J.: Metabolic footprinting in microbiology: methods and applications in functional genomics and biotechnology. Trends Biotechnol. 26, 490–497 (2008)

    Article  CAS  PubMed  Google Scholar 

  83. Lindon, J.C., Nicholson, J.K.: Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics. Annu Rev Anal Chem (Palo Alto, Calif). 1, 45–69 (2008)

    Article  CAS  Google Scholar 

  84. Kaddurah-Daouk, R., Kristal, B.S., Weinshilboum, R.M.: Metabolomics: a global biochemical approach to drug response and disease. Annu. Rev. Pharmacol. Toxicol. 48, 653–683 (2008)

    Article  CAS  PubMed  Google Scholar 

  85. Fan, X., Bai, J., Shen, P.: Diagnosis of breast cancer using HPLC metabonomics fingerprints coupled with computational methods. Conf. Proc. IEEE Eng. Med. Biol. Soc. 6, 6081–6084 (2005)

    Google Scholar 

  86. van Doorn, M., Vogels, J., Tas, A., van Hoogdalem, E.J., Burggraaf, J., Cohen, A., van der Greef, J.: Evaluation of metabolite profiles as biomarkers for the pharmacological effects of thiazolidinediones in Type 2 diabetes mellitus patients and healthy volunteers. Br. J. Clin. Pharmacol. 63, 562–574 (2007)

    Article  PubMed  CAS  Google Scholar 

  87. Clayton, T.A., Lindon, J.C., Cloarec, O., Antti, H., Charuel, C., Hanton, G., Provost, J.P., Le Net, J.L., Baker, D., Walley, R.J., et al.: Pharmaco-metabonomic phenotyping and personalized drug treatment. Nature. 440, 1073–1077 (2006)

    Article  CAS  PubMed  Google Scholar 

  88. Portilla, D., Li, S., Nagothu, K.K., Megyesi, J., Kaissling, B., Schnackenberg, L., Safirstein, R.L., Beger, R.D.: Metabolomic study of cisplatin-induced nephrotoxicity. Kidney Int. 69, 2194–2204 (2006)

    Article  CAS  PubMed  Google Scholar 

  89. Fiehn, O.: Metabolomics – the link between genotypes and phenotypes. Plant Mol. Biol. 48, 155–171 (2002)

    Google Scholar 

  90. Kind, T., Wohlgemuth, G., Lee, D.Y., Lu, Y., Palazoglu, M., Shahbaz, S., Fiehn, O.: FiehnLib: mass spectral and retention index libraries for metabolomics based on quadrupole and time-of-flight gas chromatography/mass spectrometry. Anal. Chem. 81, 10038–10048 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Becker, S., Kortz, L., Helmschrodt, C., Thiery, J., Ceglarek, U.: LC-MS-based metabolomics in the clinical laboratory. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 883-884, 68–75 (2012)

    Article  CAS  PubMed  Google Scholar 

  92. Gika, H.G., Theodoridis, G.A., Plumb, R.S., Wilson, I.D.: Current practice of liquid chromatography-mass spectrometry in metabolomics and metabonomics. J. Pharm. Biomed. Anal. 87, 12–25 (2014)

    Article  CAS  PubMed  Google Scholar 

  93. Dunn, W.B., Bailey, N.J., Johnson, H.E.: Measuring the metabolome: current analytical technologies. Analyst. 130, 606–625 (2005)

    Article  CAS  PubMed  Google Scholar 

  94. Zhang, A., Sun, H., Wang, P., Han, Y., Wang, X.: Modern analytical techniques in metabolomics analysis. Analyst. 137, 293–300 (2012)

    Article  CAS  PubMed  Google Scholar 

  95. Myint, K.T., Uehara, T., Aoshima, K., Oda, Y.: Polar anionic metabolome analysis by nano-LC/MS with a metal chelating agent. Anal. Chem. 81, 7766–7772 (2009)

    Article  CAS  PubMed  Google Scholar 

  96. Fernandez-Arroyo, S., Gomez-Martinez, A., Rocamora-Reverte, L., Quirantes-Pine, R., Segura-Carretero, A., Fernandez-Gutierrez, A., Ferragut, J.A.: Application of nanoLC-ESI-TOF-MS for the metabolomic analysis of phenolic compounds from extra-virgin olive oil in treated colon-cancer cells. J. Pharm. Biomed. Anal. 63, 128–134 (2012)

    Article  CAS  PubMed  Google Scholar 

  97. Ramautar, R., Somsen, G.W., de Jong, G.J.: CE-MS for metabolomics: developments and applications in the period 2012–2014. Electrophoresis. 36, 212–224 (2015)

    Article  CAS  PubMed  Google Scholar 

  98. Naz, S., Garcia, A., Rusak, M., Barbas, C.: Method development and validation for rat serum fingerprinting with CE-MS: application to ventilator-induced-lung-injury study. Anal. Bioanal. Chem. 405, 4849–4858 (2013)

    Article  CAS  PubMed  Google Scholar 

  99. Moraes, E.P., Ruperez, F.J., Plaza, M., Herrero, M., Barbas, C.: Metabolomic assessment with CE-MS of the nutraceutical effect of Cystoseira spp extracts in an animal model. Electrophoresis. 32, 2055–2062 (2011)

    Article  CAS  PubMed  Google Scholar 

  100. Shi, H., Vigneau-Callahan, K.E., Matson, W.R., Kristal, B.S.: Attention to relative response across sequential electrodes improves quantitation of coulometric array. Anal. Biochem. 302, 239–245 (2002)

    Article  CAS  PubMed  Google Scholar 

  101. Shi, H., Paolucci, U., Vigneau-Callahan, K.E., Milbury, P.E., Matson, W.R., Kristal, B.S.: Development of biomarkers based on diet-dependent metabolic serotypes: practical issues in development of expert system-based classification models in metabolomic studies. OMICS. 8, 197–208 (2004)

    Article  CAS  PubMed  Google Scholar 

  102. Paolucci, U., Vigneau-Callahan, K.E., Shi, H., Matson, W.R., Kristal, B.S.: Development of biomarkers based on diet-dependent metabolic serotypes: concerns and approaches for cohort and gender issues in serum metabolome studies. OMICS. 8, 209–220 (2004b)

    Article  CAS  PubMed  Google Scholar 

  103. Paolucci, U., Vigneau-Callahan, K.E., Shi, H., Matson, W.R., Kristal, B.S.: Development of biomarkers based on diet-dependent metabolic serotypes: characteristics of component-based models of metabolic serotypes. OMICS. 8, 221–238 (2004a)

    Article  CAS  PubMed  Google Scholar 

  104. Beal, M.F., Matson, W.R., Storey, E., Milbury, P., Ryan, E.A., Ogawa, T., Bird, E.D.: Kynurenic acid concentrations are reduced in Huntington’s disease cerebral cortex. J. Neurol. Sci. 108, 80–87 (1992)

    Article  CAS  PubMed  Google Scholar 

  105. Massari, F., Ciccarese, C., Santoni, M., Iacovelli, R., Mazzucchelli, R., Piva, F., Scarpelli, M., Berardi, R., Tortora, G., Lopez-Beltran, A., et al.: Metabolic phenotype of bladder cancer. Cancer Treat. Rev. 45, 46–57 (2016)

    Article  CAS  PubMed  Google Scholar 

  106. Sahu, D., Lotan, Y., Wittmann, B., Neri, B., Hansel, D.E.: Metabolomics analysis reveals distinct profiles of nonmuscle-invasive and muscle-invasive bladder cancer. Cancer Med. 6, 2106–2120 (2017)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Srivastava, S., Roy, R., Singh, S., Kumar, P., Dalela, D., Sankhwar, S.N., Goel, A., Sonkar, A.A.: Taurine – a possible fingerprint biomarker in non-muscle invasive bladder cancer: a pilot study by 1H NMR spectroscopy. Cancer Biomark. 6, 11–20 (2010)

    Google Scholar 

  108. Anghileri, L.J., Crone-Escanye, M.C., Thouvenot, P., Brunotte, F., Robert, J.: Mechanisms of gallium-67 accumulation by tumors: role of cell membrane permeability. J. Nucl. Med. 29, 663–668 (1988)

    CAS  PubMed  Google Scholar 

  109. Mycielska, M.E., Patel, A., Rizaner, N., Mazurek, M.P., Keun, H., Patel, A., Ganapathy, V., Djamgoz, M.B.: Citrate transport and metabolism in mammalian cells: prostate epithelial cells and prostate cancer. BioEssays. 31, 10–20 (2009)

    Article  CAS  PubMed  Google Scholar 

  110. Huang, Z., Lin, L., Gao, Y., Chen, Y., Yan, X., Xing, J., Hang, W.: Bladder cancer determination via two urinary metabolites: a biomarker pattern approach. Mol. Cell. Proteomics. 10(M111), 007922 (2011)

    PubMed  Google Scholar 

  111. Putluri, N., Shojaie, A., Vasu, V.T., Vareed, S.K., Nalluri, S., Putluri, V., Thangjam, G.S., Panzitt, K., Tallman, C.T., Butler, C., et al.: Metabolomic profiling reveals potential markers and bioprocesses altered in bladder cancer progression. Cancer Res. 71, 7376–7386 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Peluso, G., Nicolai, R., Reda, E., Benatti, P., Barbarisi, A., Calvani, M.: Cancer and anticancer therapy-induced modifications on metabolism mediated by carnitine system. J. Cell. Physiol. 182, 339–350 (2000)

    Article  CAS  PubMed  Google Scholar 

  113. Pelicano, H., Carney, D., Huang, P.: ROS stress in cancer cells and therapeutic implications. Drug Resist. Updat. 7, 97–110 (2004)

    Article  CAS  PubMed  Google Scholar 

  114. Shen, H., Kauvar, L., Tew, K.D.: Importance of glutathione and associated enzymes in drug response. Oncol. Res. 9, 295–302 (1997)

    CAS  PubMed  Google Scholar 

  115. Pasikanti, K.K., Esuvaranathan, K., Hong, Y., Ho, P.C., Mahendran, R., Raman Nee Mani, L., Chiong, E., Chan, E.C.: Urinary metabotyping of bladder cancer using two-dimensional gas chromatography time-of-flight mass spectrometry. J. Proteome Res. 12, 3865–3873 (2013)

    Article  CAS  PubMed  Google Scholar 

  116. Alberice, J.V., Amaral, A.F., Armitage, E.G., Lorente, J.A., Algaba, F., Carrilho, E., Marquez, M., Garcia, A., Malats, N., Barbas, C.: Searching for urine biomarkers of bladder cancer recurrence using a liquid chromatography-mass spectrometry and capillary electrophoresis-mass spectrometry metabolomics approach. J. Chromatogr. A. 1318, 163–170 (2013)

    Article  CAS  PubMed  Google Scholar 

  117. Bansal, N., Gupta, A., Mitash, N., Shakya, P.S., Mandhani, A., Mahdi, A.A., Sankhwar, S.N., Mandal, S.K.: Low- and high-grade bladder cancer determination via human serum-based metabolomics approach. J. Proteome Res. 12, 5839–5850 (2013)

    Article  CAS  PubMed  Google Scholar 

  118. Chung, K.T., Gadupudi, G.S.: Possible roles of excess tryptophan metabolites in cancer. Environ. Mol. Mutagen. 52, 81–104 (2011)

    Article  CAS  PubMed  Google Scholar 

  119. Opitz, C.A., Litzenburger, U.M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al.: An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. Nature. 478, 197–203 (2011)

    Article  CAS  PubMed  Google Scholar 

  120. Rosado, J.O., Salvador, M., Bonatto, D.: Importance of the trans-sulfuration pathway in cancer prevention and promotion. Mol. Cell. Biochem. 301, 1–12 (2007)

    Article  CAS  PubMed  Google Scholar 

  121. Zheng, Y.F., Kong, H.W., Xiong, J.H., Lv, S., Xu, G.W.: Clinical significance and prognostic value of urinary nucleosides in breast cancer patients. Clin. Biochem. 38, 24–30 (2005)

    Article  CAS  PubMed  Google Scholar 

  122. Wu, H., Xue, R., Dong, L., Liu, T., Deng, C., Zeng, H., Shen, X.: Metabolomic profiling of human urine in hepatocellular carcinoma patients using gas chromatography/mass spectrometry. Anal. Chim. Acta. 648, 98–104 (2009)

    Article  CAS  PubMed  Google Scholar 

  123. Nakano, K., Nakao, T., Schram, K.H., Hammargren, W.M., McClure, T.D., Katz, M., Petersen, E.: Urinary excretion of modified nucleosides as biological marker of RNA turnover in patients with cancer and AIDS. Clin. Chim. Acta. 218, 169–183 (1993)

    Article  CAS  PubMed  Google Scholar 

  124. Tripathi, P., Somashekar, B.S., Ponnusamy, M., Gursky, A., Dailey, S., Kunju, P., Lee, C.T., Chinnaiyan, A.M., Rajendiran, T.M., Ramamoorthy, A.: HR-MAS NMR tissue metabolomic signatures cross-validated by mass spectrometry distinguish bladder cancer from benign disease. J. Proteome Res. 12, 3519–3528 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Gatenby, R.A., Gillies, R.J.: Why do cancers have high aerobic glycolysis? Nat. Rev. Cancer. 4, 891–899 (2004)

    Article  CAS  PubMed  Google Scholar 

  126. Semenza, G.L., Artemov, D., Bedi, A., Bhujwalla, Z., Chiles, K., Feldser, D., Laughner, E., Ravi, R., Simons, J., Taghavi, P., et al.: ‘The metabolism of tumours’: 70 years later. Novartis Found. Symp. 240, 251–260 (2001) discussion 260-254

    CAS  PubMed  Google Scholar 

  127. Liang, Q., Zhang, G., Li, W., Wang, J., Sheng, S.: Comparison of the diagnostic performance of fluorescence in situ hybridization (FISH), nuclear matrix protein 22 (NMP22), and their combination model in bladder carcinoma detection: a systematic review and meta-analysis. Onco. Targets. Ther. 12, 349–358 (2019)

    Article  CAS  PubMed  Google Scholar 

  128. Hajdinjak, T.: UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urol. Oncol. 26, 646–651 (2008)

    Article  CAS  PubMed  Google Scholar 

  129. Horstmann, M., Patschan, O., Hennenlotter, J., Senger, E., Feil, G., Stenzl, A.: Combinations of urine-based tumour markers in bladder cancer surveillance. Scand. J. Urol. Nephrol. 43, 461–466 (2009)

    Article  PubMed  Google Scholar 

  130. Todenhofer, T., Hennenlotter, J., Esser, M., Mohrhardt, S., Tews, V., Aufderklamm, S., Gakis, G., Kuehs, U., Stenzl, A., Schwentner, C.: Combined application of cytology and molecular urine markers to improve the detection of urothelial carcinoma. Cancer Cytopathol. 121, 252–260 (2013)

    Article  PubMed  CAS  Google Scholar 

  131. He, H., Han, C., Hao, L., Zang, G.: ImmunoCyt test compared to cytology in the diagnosis of bladder cancer: a meta-analysis. Oncol. Lett. 12, 83–88 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. Shao, C.H., Chen, C.L., Lin, J.Y., Chen, C.J., Fu, S.H., Chen, Y.T., Chang, Y.S., Yu, J.S., Tsui, K.H., Juo, C.G., et al.: Metabolite marker discovery for the detection of bladder cancer by comparative metabolomics. Oncotarget. 8, 38802–38810 (2017)

    Article  PubMed  PubMed Central  Google Scholar 

  133. Liu, X., Cheng, X., Liu, X., He, L., Zhang, W., Wang, Y., Sun, W., Ji, Z.: Investigation of the urinary metabolic variations and the application in bladder cancer biomarker discovery. Int. J. Cancer. 143, 408–418 (2018)

    Article  CAS  PubMed  Google Scholar 

  134. Loras, A., Trassierra, M., Sanjuan-Herraez, D., Martinez-Bisbal, M.C., Castell, J.V., Quintas, G., Ruiz-Cerda, J.L.: Bladder cancer recurrence surveillance by urine metabolomics analysis. Sci. Rep. 8, 9172 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Wittmann, B.M., Stirdivant, S.M., Mitchell, M.W., Wulff, J.E., McDunn, J.E., Li, Z., Dennis-Barrie, A., Neri, B.P., Milburn, M.V., Lotan, Y., et al.: Bladder cancer biomarker discovery using global metabolomic profiling of urine. PLoS One. 9, e115870 (2014)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Jin, F., Shahid, M., Kim, J. (2021). Research Progress of Urine Biomarkers in the Diagnosis, Treatment, and Prognosis of Bladder Cancer. In: Baptista Carreira dos Santos, H.M. (eds) Translational Urinomics. Advances in Experimental Medicine and Biology(), vol 1306. Springer, Cham. https://doi.org/10.1007/978-3-030-63908-2_5

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