Molecular analysis of transitional cell carcinoma of the upper urinary tract using CDNA microarray

ABSTRACT

To date, molecular evidence studies for transitional cell carcinoma [TCC], using the microarray technology, are focusing on TCC of the urinary bladder and no studies have been performed on TCC of the upper urinary tract [UUT]. This study was conducted to monitor the gene expression profiles between transitional cell carcinoma of the upper urinary tract [TCC-UUT] and normal urothelium of UUT. cDNA microarrays were prepared by spotting PCR products of 14.551 human genes onto specially treated glass slides to analyze gene expression among 9 eases of TCC-UUT and 8 cases of normal urothelium in order to study the molecular basis of TCC-UUT development. Quantitative real time polymerase chain reaction [QRT-PCR] was performed for selected genes to validate the results of mieroarray hybridization. After supervised analysis of the microarray data, there was at least a 2.5-fold difference in the expression between TCC-UUT and normal urothelium in 55 genes. Significant up-regulation of 27 genes was associated with cases of TCC-UUT, including matrix degradation-related genes, as well as genes related to growth factors, immunology, cell-cycling and angiogenesis. Conversely, significant down-regulation of 28 genes was associated with eases of TCC-UUT including genes involved in epithelial cell dedifferentiation and keratinization, as well as genes related to cell adhesion and apoptosis. Such gene profiling studies can identify new molecular markers for early diagnosis and disease follow-up, it also allows the classification of tumors into subclasses assisting in disease diagnosis and prognosis, as well as in treatment selection