Prediction of recurrence in Ta urothelial cell carcinoma by real-time quantitative PCR analysis: A microarray validation study
Iman J. Schultz
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorKenneth Wester
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, Uppsala, Sweden
Search for more papers by this authorHuub Straatman
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorLambertus A. Kiemeney
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorMarko Babjuk
Department of Urology, General Faculty Hospital, Charles University, Prague, Czech Republic
Search for more papers by this authorJaroslav Mares
Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic
Search for more papers by this authorJohanner L. Willems
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorCorresponding Author
Dorine W. Swinkels
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Fax: +31-243541743
AKC/441, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The NetherlandsSearch for more papers by this authorJ. Alfred Witjes
Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorJacques B. de Kok
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorPer-Uno Malmström
Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
Search for more papers by this authorIman J. Schultz
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorKenneth Wester
Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University Hospital, Uppsala, Sweden
Search for more papers by this authorHuub Straatman
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorLambertus A. Kiemeney
Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorMarko Babjuk
Department of Urology, General Faculty Hospital, Charles University, Prague, Czech Republic
Search for more papers by this authorJaroslav Mares
Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic
Search for more papers by this authorJohanner L. Willems
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorCorresponding Author
Dorine W. Swinkels
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Fax: +31-243541743
AKC/441, Radboud University Nijmegen Medical Center, P.O. Box 9101, 6500 HB Nijmegen, The NetherlandsSearch for more papers by this authorJ. Alfred Witjes
Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorJacques B. de Kok
Department of Clinical Chemistry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
Search for more papers by this authorPer-Uno Malmström
Department of Surgical Sciences, Uppsala University Hospital, Uppsala, Sweden
Search for more papers by this authorAbstract
Accurate prediction of tumor recurrence in patients with superficial urothelial cell carcinoma (UCC) might result in a significant reduction of invasive follow-up cystoscopies. A recent study identified a panel of 26 genes from a large cDNA microarray analysis of bladder tumors that discriminated between early- and late-recurring patients with superficial Ta tumors (Dyrskjøt et al., Nat Genet 2003;33:90–6). We aimed to validate this panel of genes in 44 primary Ta UCCs (23 and 21 tumors from patients with short or prolonged recurrence-free periods, respectively), by real-time quantitative PCR. Statistical analysis showed marginal significant different mRNA expression levels between the 2 patient groups. To evaluate a supplementary effect of genes for the identification of patients with short or prolonged recurrence-free intervals, forward logistic regression analysis was applied. This revealed that a combination of the expression profiles of the genes HNRPK, LTB4DH and ANP32B resulted in the best performance, although the combination only marginally increased the predictive value of HNRPK alone. Comparing the receiver-operating-characteristic curves for HNRPK expression among patients with short or prolonged recurrence-free periods, revealed an area under the curve of 0.696 (95% CI, 0.537–0.855). Using the median HNRPK expression level as cut-off, a sensitivity of 69.6% and a specificity of 71.4% were obtained for the identification of patients with short or prolonged recurrence-free periods, respectively. In conclusion, we were not able to confirm the microarray gene expression pattern of the 26 genes shown by Dyrskjøt et al. The discovery of accurate recurrence predictive markers, therefore, remains a challenge. © 2006 Wiley-Liss, Inc.
Supporting Information
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