Abstract
Objective
To evaluate urinary Aurora A Kinase (AURKA) mRNA expression as a diagnostic biomarker for urothelial bladder cancer (UBC).
Methods
One hundred and eighty-eight urine samples from patients with UBC (n = 122) and controls with hematuria (n = 66) were investigated. AURKA expression was quantified using real-time PCR and compared with voided urinary cytology. Associations with stage and grade were assessed. The area under curve was used to quantify the predictive accuracy (PA).
Results
The sensitivity and the specificity of AURKA for UBC were 83.6 and 65.2 %, respectively (PA = 74.4 %). Among those with detectable AURKA, the quantity of expression was similar in cases and controls. Compared with Ta, tumors staged T1 and T2 showed a 9.31-fold and 4.78-fold increased AURKA expression (p = 0.034), respectively. Further, high-grade tumors showed 5.33-fold higher expression levels than low-grade tumors (p = 0.031). AURKA and urinary cytology showed similar overall PA for UBC detection (74.4 vs. 72.1 %, p = 0.588). For low-grade tumors, AURKA was more accurate (72.5 vs. 59.0 %, p = 0.004), while cytology was more accurate for high-grade lesions (76.8 vs. 89.1 %, p = 0.011).
Conclusions
In patients with hematuria, AURKA is associated with the presence and grade of UBC, suggesting a role as diagnostic and prognostic biomarker. As AURKA is more accurate in low-grade tumors but less accurate in high-grade tumors than urinary cytology, both could be complementary in detecting UBC.
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References
Ferlay J, Parkin DM, Steliarova-Foucher E (2010) Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer 46:765–781
Sievert KD, Amend B, Nagele U, Schilling D, Bedke J, Horstmann M, Hennenlotter J, Kruck S, Stenzl A (2009) Economic aspects of bladder cancer: what are the benefits and costs? World J Urol 27:295–300
Karaoglu I, van der Heijden AG, Witjes JA (2013) The role of urine markers, white light cystoscopy and fluorescence cystoscopy in recurrence, progression and follow-up of non-muscle invasive bladder cancer. World J Urol. doi:10.1007/s00345-013-1035-1 (epub ahead of print)
Kamat AM, Hegarty PK, Gee JR, Clark PE, Svatek RS, Hegarty N, Shariat SF, Xylinas E, Schmitz-Drager BJ, Lotan Y, Jenkins LC, Droller M, van Rhijn BW, Karakiewicz PI (2013) ICUD-EAU international consultation on bladder cancer 2012: screening, diagnosis, and molecular markers. Eur Urol 63:4–15
Horstmann M, Bontrup H, Hennenlotter J, Taeger D, Weber A, Pesch B, Feil G, Patschan O, Johnen G, Stenzl A, Bruning T (2010) Clinical experience with survivin as a biomarker for urothelial bladder cancer. World J Urol 28:399–404
Horstmann M, Todenhofer T, Hennenlotter J, Aufderklamm S, Mischinger J, Kuehs U, Gakis G, Stenzl A, Schwentner C (2013) Influence of age on false positive rates of urine-based tumor markers. World J Urol 31:935–940
Miyake M, Goodison S, Rizwani W, Ross S, Bart Grossman H, Rosser CJ (2012) Urinary BTA: indicator of bladder cancer or of hematuria. World J Urol 30:869–873
Tan LB, Chen KT, Yuan YC, Liao PC, Guo HR (2010) Identification of urine PLK2 as a marker of bladder tumors by proteomic analysis. World J Urol 28:117–122
Fraizer GC, Diaz MF, Lee IL, Grossman HB, Sen S (2004) Aurora-A/STK15/BTAK enhances chromosomal instability in bladder cancer cells. Int J Oncol 25:1631–1639
Yamamoto Y, Matsuyama H, Kawauchi S, Furuya T, Liu XP, Ikemoto K, Oga A, Naito K, Sasaki K (2006) Biological characteristics in bladder cancer depend on the type of genetic instability. Clin Cancer Res 12:2752–2758
Katayama H, Sasai K, Kawai H, Yuan ZM, Bondaruk J, Suzuki F, Fujii S, Arlinghaus RB, Czerniak BA, Sen S (2004) Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 36:55–62
Sen S, Zhou H, Zhang RD, Yoon DS, Vakar-Lopez F, Ito S, Jiang F, Johnston D, Grossman HB, Ruifrok AC, Katz RL, Brinkley W, Czerniak B (2002) Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 94:1320–1329
Mhawech-Fauceglia P, Fischer G, Beck A, Cheney RT, Herrmann FR (2006) Raf1, Aurora-A/STK15 and E-cadherin biomarkers expression in patients with pTa/pT1 urothelial bladder carcinoma; a retrospective TMA study of 246 patients with long-term follow-up. Eur J Surg Oncol 32:439–444
Bufo P, Sanguedolce F, Tortorella S, Cormio L, Carrieri G, Pannone G (2010) Expression of mitotic kinases phospho-aurora A and aurora B correlates with clinical and pathological parameters in bladder neoplasms. Histol Histopathol 25:1371–1377
Lei Y, Yan S, Ming-De L, Na L, Rui-Fa H (2011) Prognostic significance of Aurora-A expression in human bladder cancer. Acta Histochem 113:514–518
Park HS, Park WS, Bondaruk J, Tanaka N, Katayama H, Lee S, Spiess PE, Steinberg JR, Wang Z, Katz RL, Dinney C, Elias KJ, Lotan Y, Naeem RC, Baggerly K, Sen S, Grossman HB, Czerniak B (2008) Quantitation of Aurora kinase A gene copy number in urine sediments and bladder cancer detection. J Natl Cancer Inst 100:1401–1411
Compérat E, Bieche I, Dargere D, Laurendeau I, Vieillefond A, Benoit G, Vidaud M, Camparo P, Capron F, Verret C, Cussenot O, Bedossa P, Paradis V (2008) Gene expression study of Aurora-A reveals implication during bladder carcinogenesis and increasing values in invasive urothelial cancer. Urology 72:873–877
Compérat E, Camparo P, Haus R, Chartier-Kastler E, Radenen B, Richard F, Capron F, Paradis V (2007) Aurora-A/STK-15 is a predictive factor for recurrent behaviour in non-invasive bladder carcinoma: a study of 128 cases of non-invasive neoplasms. Virchows Arch 450:419–424
Koss LG, Melamed MR (2006) Koss’ diagnostic cytology and its histopathologic bases, vol 1. Lippincott Williams & Wilkins, Philadelphia, pp 738–777
Bangma CH, Loeb S, Busstra M, Zhu X, El Bouazzaoui S, Refos J, Van Der Keur KA, Tjin S, Franken CG, van Leenders GJ, Zwarthoff EC, Roobol MJ (2013) Outcomes of a bladder cancer screening program using home hematuria testing and molecular markers. Eur Urol 64:41–47
Bensalah K, Montorsi F, Shariat SF (2007) Challenges of cancer biomarker profiling. Eur Urol 52:1601–1609
Mazzorana M, Montoya G, Mortuza GB (2011) The centrosome: a target for cancer therapy. Curr Cancer Drug Targets 11:600–612
Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL Jr, Golemis EA (2013) Aurora A kinase (AURKA) in normal and pathological cell division. Cell Mol Life Sci 70:661–687
Meraldi P, Honda R, Nigg EA (2002) Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53 −/− cells. EMBO J 21:483–492
Miyake M, Goodison S, Giacoia EG, Rizwani W, Ross S, Rosser CJ (2012) Influencing factors on the NMP-22 urine assay: an experimental model. BMC Urol 12:23–28
Lotan Y, Shariat SF, Schmitz-Drager BJ, Sanchez-Carbayo M, Jankevicius F, Racioppi M, Minner SJ, Stohr B, Bassi PF, Grossman HB (2010) Considerations on implementing diagnostic markers into clinical decision making in bladder cancer. Urol Oncol 28:441–448
Mhawech-Fauceglia P, Fischer G, Alvarez V Jr, Ahmed A, Herrmann FR (2007) Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysis. BJU Int 100:1182–1187
Babjuk M, Burger M, Zigeuner R, Shariat SF, van Rhijn BW, Comperat E, Sylvester RJ, Kaasinen E, Bohle A, Palou Redorta J, Roupret M (2013) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 64:639–653
Faba OR, Palou J, Breda A, Villavicencio H (2012) High-risk non-muscle-invasive bladder cancer: update for a better identification and treatment. World J Urol 30:833–840
Zhou N, Singh K, Mir MC, Parker Y, Lindner D, Dreicer R, Ecsedy JA, Zhang Z, Teh BT, Almasan A, Hansel DE (2013) The investigational aurora kinase a inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo. Clin Cancer Res 19:1717–1728
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The authors declare that they have no conflict of interest.
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The study was approved by the local ethics committee and was therefore performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.
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de Martino, M., Shariat, S.F., Hofbauer, S.L. et al. Aurora A Kinase as a diagnostic urinary marker for urothelial bladder cancer. World J Urol 33, 105–110 (2015). https://doi.org/10.1007/s00345-014-1267-8
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DOI: https://doi.org/10.1007/s00345-014-1267-8