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Clinical Chemistry 0: clinchem.2007.091363v1, 2007; 10.1373/clinchem.2007.091363
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Right arrow Molecular Diagnostics and Genetics

Received on May 3, 2007
Accepted on August 31, 2007

Molecular Diagnostics and Genetics

Detailed Technical Analysis of Urine RNA-Based Tumor Diagnostics Reveals ETS2/Urokinase Plasminogen Activator to Be a Novel Marker for Bladder Cancer

Merle Hanke 1, Ingo Kausch 2, Gerlinde Dahmen 3, Dieter Jocham 2, Jens M. Warnecke 1*

1 Kompetenzzentrum fuer Drug Design und Target Monitoring, Luebeck, Germany; Institut fuer Molekulare Medizin, Luebeck, Germany
2 Klinik und Poliklinik für Urologie, Luebeck, Germany
3 Institut fuer Medizinische Biometrie und Statistik, UK-S-H, Campus Luebeck, Luebeck, Germany

* To whom correspondence should be addressed. E-mail: warnecke{at}imm.uni-luebeck.de.

Background: The noninvasive detection of RNA tumor markers in body fluids represents an attractive diagnostic option, but diagnostic performance of tissue-derived markers is often poorer when measured in body fluids rather than in tumors. We aimed to develop a procedure for measurement of tumor RNA in urine that would minimize donor-dependent influences on the results.

Methods: RNA isolated from urinary cell pellet, cell-depleted fraction, and whole urine was quantified by quantitative reverse transcription–PCR. The donor-dependent influence of urine background on individual steps of the standardized procedure was analyzed using an external RNA standard. Using a test set of samples from 61 patients with bladder cancer and 37 healthy donors, we compared 4 putative RNA tumor markers identified in whole urine with 5 established, tissue-derived RNA tumor markers for the detection of bladder cancer.

Results: Of the markers analyzed by this system, the RNA ratio of v-ets erythroblastosis virus E26 oncogene homolog 2 (avian; ETS2) to urokinase plasminogen activator (uPA) enabled the most specific (100%) and sensitive (75.4%) detection of bladder cancer from whole urine, with an area under the curve of 0.929 (95% CI 0.882–0.976).

Conclusions: The described methodology for RNA marker detection in urine appears to be clinically applicable. The ratio of ETS2 mRNA to uPA mRNA in urine appears to have potential as a marker for bladder cancer.






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Copyright © 2007 by the American Association for Clinical Chemistry.