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Tumor Biology |
Departments of Clinical Chemistry [J. B. d. K., R. W. R., D. W. S.], Experimental Urology [G. W. V., D. H., L. A. K., T. W. A., J. A. S.], and Epidemiology and Biostatistics [L. A. K.], University Medical Centre Nijmegen, 6500 HB Nijmegen, the Netherlands
We identified DD3PCA3 as one of the most prostate cancer-specific genes at present (M. J. Bussemakers et al. Cancer Res., 59: 59755979, 1999). Consequently, DD3PCA3 is an interesting candidate for use as a diagnostic and/or prognostic marker. In this study we developed a method for the accurate quantification of DD3PCA3 mRNA, using real-time quantitative reverse transcription-PCR. DD3PCA3 was expressed at low levels in normal prostate but not in 21 selected other normal tissues, blood, or 39 tumor samples other than prostate. The diagnostic and prognostic value of DD3PCA3 in normal, hyperplastic, and malignant prostate tissues was determined and compared with another promising tumor marker for prostate cancer, telomerase reverse transcriptase (hTERT gene), the expression of which is related to telomerase activity. Sensitivity and specificity estimates for both genes were calculated as the area under the receiver-operating characteristics curve (AUC-ROC). DD3PCA3 (AUC-ROC, 0.98) demonstrated better diagnostic efficacy than hTERT (AUC-ROC, 0.88). Moreover, the median increase in mRNA expression in tumor tissues compared with nonmalignant prostate tissues was much higher for DD3PCA3 (34-fold) than for hTERT (6-fold). In tumor tissues, the median expression of DD3PCA3 was much higher than hTERT (5849 versus 10 normalized mRNA copies). A significant relationship was observed only between tumor stage and hTERT gene expression. We conclude that expression of the DD3PCA3 gene is a very sensitive and specific marker for the detection of prostate tumor cells in a high background of normal (prostate) cells. Consequently, DD3 measurements may be used for clinical application in prostate needle biopsies or bodily fluids such as blood, ejaculate, urine, or prostate massage fluid.
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