Prediction and diagnosis of bladder cancer recurrence based on urinary content of hTERT, SENP1, PPP1CA, and MCM5 transcripts

BMC Cancer

Research Article

Helle Toldbod¹  Torben F Ørntoft²  Lars Dyrskjøt²  Anne Sofie Brems-Eskildsen²  Pia P Munksgaard²  Francisco Mansilla²  Michael Borre³  Karsten Zieger³  Russell Higuchi⁴  Cherie Holcomb⁴ 

[1] Department of Hematology, Aarhus University Hospital, Aarhus, Denmark;Department of Molecular Medicine, Aarhus University Hospital, Skejby, Denmark;Department of Urology, Aarhus University Hospital, Skejby, Denmark;Roche Molecular Systems, Pleasanton, California, USA;

关键词: Bladder Cancer;    Recurrence Free Survival;    hTERT mRNA;    Urinary Content;    Bladder Cancer Recurrence;   

DOI  :  10.1186/1471-2407-10-646

 received in 2010-06-03, accepted in 2010-11-24,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundIdentification of urinary biomarkers for detection of bladder cancer recurrence would be beneficial to minimize the frequency of cystoscopy. Our objective was to determine the usability of urine content of mRNA in the detection and prediction of bladder cancer recurrence.MethodsWe analyzed 123 prospectively cross-sectional collected urine samples from 117 patients with bladder cancer (12 incident cancers and 111 control visits). We used biopsies from cystoscopies as diagnostic criteria for recurrence, and followed the patients for a median time of 28.5 months (range 0-44 months). We measured the levels of hTERT, SENP1, PPP1CA, and MCM5 mRNA in urine by q-RT- PCR.ResultsWe found significant differences in urinary content of hTERT (p < 0.001), SENP1 (p < 0.001), MCM5 (p < 0.001), and PPP1CA (p < 0.001) transcripts, when comparing urine samples from patients with and without tumor present in the bladder. We obtained sensitivity and specificity values for hTERT: 63/73, SENP1: 56/78, MCM5: 63/66, and PPP1CA: 69/63, respectively. Including follow-up data resulted in sensitivity and specificity values for hTERT: 62/84, SENP1:53/84, MCM5: 61/73, and PPP1CA: 65/66. Interestingly, at non-tumor visits the urinary content of especially hTERT (p = 0.0001) and MCM5 (p = 0.02) were significantly associated with subsequent tumour recurrence. Combining the markers with cytology improved the detection. The best combination was hTERT and cytology with a sensitivity of 71% and a specificity of 86% after follow-up. Further prospective validation or registration studies needs to be carried out before clinical use.ConclusionsWe could use the urinary content of hTERT, SENP1, PPP1CA, and MCM5 to detect bladder cancer recurrence. All markers showed a higher sensitivity than cytology. The detection rate improved when including cytology results, but also the combination of hTERT and MCM5 increased the detection rate. Furthermore, hTERT and MCM5 levels predicted subsequent tumor recurrences.

【 授权许可】

Unknown   
© Brems-Eskildsen et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.