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

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.

基于芯片的基因表达谱分析：尿路上皮癌（UC）可发生于尿路上皮通路的任意部位，涵盖尿道、膀胱、输尿管及肾盂。尽管不同部位起源的肿瘤形态学特征相似，但上尿路（输尿管与肾盂）与下尿路（膀胱与尿道）尿路上皮癌的基因表达谱是否具有一致性尚不明确，尤其考虑到二者胚胎起源存在差异。鉴于肿瘤生物学特征的差异可能指导差异化的筛查与治疗策略，本研究旨在探讨肾盂尿路上皮癌（rUC）与膀胱尿路上皮癌（bUC）之间的关联。本研究收集了bUC患者的新鲜肿瘤组织（n=10），同时收集了因非UC疾病接受膀胱切除术患者的膀胱良性黏膜组织（n=7）作为对照。采用高通量Affymetrix基因表达微阵列芯片检测上述样本的基因表达谱，并结合本团队既往发表研究中使用的rUC样本（n=14）与正常肾组织样本（n=14）的基因表达谱，通过生物信息学方法开展对比分析。采用无监督分析方法时，rUC与bUC样本无法区分；而采用有监督分析方法时，仅鉴定出极少数潜在差异表达基因，且这些差异主要集中于单一通路——氯离子结合活性通路，该通路在rUC中的激活频率高于bUC。本研究发现，上尿路与下尿路尿路上皮癌的基因表达谱高度相似，提示两类肿瘤的发生发展可能共享相似的致病机制。上述通路中基因的差异表达或许可为上尿路肿瘤的检测提供潜在新方向。本研究收集了下尿路（膀胱）尿路上皮细胞癌组织样本及正常对照样本，将其基因表达谱与本团队既往已发表数据集的样本基因表达谱进行比较。本数据集无技术重复样本。