<p>INTRODUCTION: Parallel gene-expression monitoring is a powerful tool for analyzing relationships among tumors, discovering new tumor subgroups, assigning tumors to pre-defined classes, identifying co-regulated or tumor stage-specific genes and predicting disease outcome. Previous gene expression studies have focused on identifying differences between tumor samples of the same type.</p>
<p>AIM OF STUDY: Using a reverse engineering approach, we searched for common expression profiles among tumor samples. We analyzed the gene expression profile of bladder cancer (BC) and determined the differentially expressed (DE) genes between cancer and healthy tissue, using cross-platform comparisons.</p>
<p>MATERIALS AND METHODS: We performed cDNA microarray analysis, comprising both in-house experimental and publicly available GEO microarray data. In total, our pooled microarray analysis was composed of 17 control samples (n=5, for the CodeLink platform; and n=12, for the remaining microarray platforms) and 129 BC samples (n=10, for the CodeLink platform; and n=119, for the remaining microarray platforms). Tumor samples were separated into the following groups: Ta/T1 without CIS; Ta/T1 with CIS; Ta-grade 1; Ta-grade 3; T1-grade2; T1-grade 3; T2-grade 2-4. Each group was compared against all control samples and the DE genes were identified. Data were clustered with different algorithms.</p>
<p>RESULTS:</p>
<p>A two-sample T-test analysis for all tumor samples vs. all normal samples, revealed 434 DE genes between the two tissue groups. Hierarchical clustering (HCL) showed a clear distinction among tumor samples. In total, 17 genes appeared to be commonly expressed among all BC samples: BMP4, CRYGD, DBH, GJB1, KRT83, MPZ, NHLH1, TACR3, ACTC1, MFAP4, SPARCL1, TAGLN, TPM2, CDC20, LHCGR, TM9SF1 and HCCS. Three groups of genes were down-regulated in all samples: BMP4, CRYGD, DBH, GJB1, KRT83, MPZ, NHLH1, TACR3 in cluster 79; ACTC1, MFAP4, SPARCL1, TAGLN in cluster 81; and TPM2 in cluster 82. CDC20, TM9SF1 and HCCS appeared to be simultaneously over-expressed in all tumor groups. LHCGR was differentially expressed in 108/129 (83.7%) of the BC samples.</p>
<p>DISCUSSION: Through this investigation we were able to identify several important factors that warrant further investigation both as prognostic markers and as therapeutic targets. Such approaches may provide a better insight into tumorigenesis and tumor progression.</p
