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Comparative Gene Expression Profiling Analysis of Urothelial Carcinoma of Renal Pelvis and Bladder

ABSTRACT: Expression profiling by arrays Urothelial carcinoma (UC) can arise at any location along the urothelial tract, including the urethra, bladder, ureter or renal pelvis. Although tumors arising in these various locations demonstrate similar morphology, it is unclear whether the gene expression profiles are similar in the upper tract (ureter and renal pelvis) or in the lower tract (bladder and urethra) carcinomas, especially given their different embryologic origins. As differences may facilitate potentially different screening and treatment modalities, we sought to examine the relationship between urothelial carcinoma of the renal pelvis (rUC) and urothelial carcinoma of the bladder (bUC). Fresh tumor tissue was collected from patients with bUC (n=10) and benign mucosa from the bladder (n=7) was collected from individuals undergoing resection for non-UC conditions for comparison. Gene expression profiles from these samples were determined using high-throughput Affymetrix gene expression microarray chips. Bioinformatic approaches were used to compare gene expression profiles of these samples and those of rUC (n= 14) and normal kidney (n=14) that were mostly used in our previous publication. Using unsupervised analytic approaches, rUC and bUC were indistinguishable. When supervised analytic approach was used, a very small number of potentially differentially expressed genes was identified; these differences were most likely to be limited to a single pathway - the chloride ion binding activity pathway -which was more frequently activated in rUC than in bUC. We found that the gene expression profiles of UCs from the upper and lower tract were extremely similar, suggesting that similar pathogenic mechanisms likely function in the development of these tumors. The differential expression of genes in the identified pathway may represent a potential new avenue for detection of upper tract tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE24152 | GEO | 2010/12/31

SECONDARY ACCESSION(S): PRJNA130035

REPOSITORIES: GEO

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Project description:Expression profiling by arrays Urothelial carcinoma (UC) can arise at any location along the urothelial tract, including the urethra, bladder, ureter or renal pelvis. Although tumors arising in these various locations demonstrate similar morphology, it is unclear whether the gene expression profiles are similar in the upper tract (ureter and renal pelvis) or in the lower tract (bladder and urethra) carcinomas, especially given their different embryologic origins. As differences may facilitate potentially different screening and treatment modalities, we sought to examine the relationship between urothelial carcinoma of the renal pelvis (rUC) and urothelial carcinoma of the bladder (bUC). Fresh tumor tissue was collected from patients with bUC (n=10) and benign mucosa from the bladder (n=7) was collected from individuals undergoing resection for non-UC conditions for comparison. Gene expression profiles from these samples were determined using high-throughput Affymetrix gene expression microarray chips. Bioinformatic approaches were used to compare gene expression profiles of these samples and those of rUC (n= 14) and normal kidney (n=14) that were mostly used in our previous publication. Using unsupervised analytic approaches, rUC and bUC were indistinguishable. When supervised analytic approach was used, a very small number of potentially differentially expressed genes was identified; these differences were most likely to be limited to a single pathway - the chloride ion binding activity pathway -which was more frequently activated in rUC than in bUC. We found that the gene expression profiles of UCs from the upper and lower tract were extremely similar, suggesting that similar pathogenic mechanisms likely function in the development of these tumors. The differential expression of genes in the identified pathway may represent a potential new avenue for detection of upper tract tumors. Tissue samples with urothelial cell carcinoma from lower tract (bladder) as well as normal references were collected and the gene expression profiles were compared with gene expression profiles of samples in our previously published data set . No technical replicates.

Project description:Prognostic biomarkers including microRNAs(miRNAs) and genes in upper tract urothelial carcinomas (UTUCs) originating from the renal pelvis and ureter account for only 5% to 10% of all UCs, but this figure is markedly higher in Taiwan, where it can reach up to 30%. By using next-generation sequencing (NGS), we analysed two pairs of renal pelvis tumours and adjacent normal urothelial tissues to screen miRNAs and messenger RNAs. By combining bioinformatics analysis from miRmap, Gene Expression Omnibus (GEO), and Oncomine and Ingenuity® Pathway Analysis databases, we identified candidate genes. To search upstream miRNAs with exact target binding sites, we used miRmap, TargetScan, and miRDB to enforce evidence. Then, we clarified gene and protein expression through an in vitro study. After interaction of the selected target genes obtained using the NGS and miRmap methods were analysed through a Venn diagram analysis, six potential genes—namely, PDE5A, RECK, ZEB2, NCALD, PLCXD3, CYBRD1—presenting significant differences were distinguished. Further analysis of gene expression indicated lower expression of that PDE5A, RECK, ZEB2, and CYBRD1 in bladder cancer tissue than in normal bladder mucosa, which indicated that PDE5A, RECK, ZEB2, and CYBRD1 may act as tumour suppressors in UTUC. In addition, we identified putative oncomiRs in miR-181c-5p target sites on PDE5A, miR-200c-3p target sites on RECK, and miR-200bc-3p/429 target sites on ZEB2. Compared with normal tissue, lower PDE5A expression in tumour specimens was demonstrated in paired UTUC tissues (normal and tumour) from 20 patients. Our findings suggest that both candidate miRNAs and regulated genes may play crucial roles in UTUC progression. We propose that these markers may be potential targets in both diagnostic and therapeutic strategies as clarified by in vitro and in vivo experiments. PDE5A also potentially presents tumour suppressor genes, as identified by comparing the expression between normal and tumour specimens from 10 patients.

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Comparative Gene Expression Profiling Analysis of Urothelial Carcinoma of Renal Pelvis and Bladder

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