BERKELEY, CA (UroToday.com) - In our recent paper published in BMC Medical Genomics, we examined the gene expression profiles of tumor and normal tissue samples from patients who had urothelial carcinoma at either upper tract (ureter and renal pelvis) or lower tract (bladder and urethra) in an attempt to answer an important question of whether the urothelial carcinoma from the upper and lower tracts are the same entity at genomic level.
Controversial statements existed about their relations in the literature. This study will clarify some of the clouds over these controversies at genome level.
By using Affymetrix’s most popular arrays (Hgu133plus2) interrogating virtually all annotated genes in human genome, we compared the expression profiles of a total of 43 samples, including 10 urothelial carcinomas arising from the lower tract in the bladder, 13 urothelial carcinomas from renal pelvis (of upper tract), together with 7 samples of benign bladder urothelium and 13 samples of benign kidney. Without knowledge of the sample classes, we found that the normal samples can be easily separated from the tumor samples, indicating the expression profiles of normal and tumor samples are very different. However, the urothelial carcinoma from bladder and urothelial carcinoma from renal pelvis are well mixed with each other. The same is true when we use the top genes having expressions most varied among the samples in order to group them. With knowledge of the sample classes, when we compare the expression levels of urothelial carcinomas from the two locations gene-by-gene, we found that only a limited number of genes seem to be differentially expressed between them. Our study thus confirms that the two seemingly different entities of tumors are virtually the same at genomic level; the differences between them are very limited, probably to one single gene pathway. Therefore, we infer that urothelial carcinoma from upper and lower urinary tracts are probably of same origins with same genetic abnormalities, supporting the idea that they can be treated in the same way, especially when molecular chemotherapies are used to treat the patients. We acknowledge that increased sample size is needed to expand the study. It will be interesting to confirm the differences in the identified pathway in the upper and lower tract urothelial carcinoma through laboratory experiments at both transcript level and at protein level, and to go a step further of exploring the phenotypic implications from this genotypic differences.
Zhongfa Zhang, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.