Gene Expression in the Urinary Bladder

Abstract

The presence of carcinoma in situ (CIS) lesions in the urinary bladder is associated with a high risk of disease progression to a muscle invasive stage. In this study, we used microarray expression profiling to examine the gene expression patterns in superficial transitional cell carcinoma (sTCC) with surrounding CIS (13 patients), without surrounding CIS lesions (15 patients), and in muscle invasive carcinomas (mTCC; 13 patients). Hierarchical cluster analysis separated the sTCC samples according to the presence or absence of CIS in the surrounding urothelium. We identified a few gene clusters that contained genes with similar expression levels in transitional cell carcinoma (TCC) with surrounding CIS and invasive TCC. However, no close relationship between TCC with adjacent CIS and invasive TCC was observed using hierarchical cluster analysis. Expression profiling of a series of biopsies from normal urothelium and urothelium with CIS lesions from the same urinary bladder revealed that the gene expression found in sTCC with surrounding CIS is found also in CIS biopsies as well as in histologically normal samples adjacent to the CIS lesions. Furthermore, we also identified similar gene expression changes in mTCC samples. We used a supervised learning approach to build a 16-gene molecular CIS classifier. The classifier was able to classify sTCC samples according to the presence or absence of surrounding CIS with a high accuracy. This study demonstrates that a CIS gene expression signature is present not only in CIS biopsies but also in sTCC, mTCC, and, remarkably, in histologically normal urothelium from bladders with CIS. Identification of this expression signature could provide guidance for the selection of therapy and follow-up regimen in patients with early stage bladder cancer.

Decorin Antagonizes IGF Receptor I (IGF-IR) Function by Interfering with IGF-IR Activity and Attenuating Downstream Signaling

“…Using the ONCOMINE program (50, 51), we have analyzed decorin mRNA levels in available microarray data sets and found that decorin expression is considerably reduced in urothelial carcinoma vis-à-vis normal bladder tissues in two independent data sets (54,55). In addition, by immunohistochemical analysis of low and high grade bladder cancer specimens, we discovered that decorin expression is almost totally lost in the tumor stroma compared with normal bladder and inversely correlates with IGF-IR levels, whose expression is markedly increased with bladder cancer progression.…”

PTPD1 Supports Receptor Stability and Mitogenic Signaling in Bladder Cancer Cells

“…PTPD1 mRNA is up-regulated in several forms of cancer (27,28). Up-regulated EGFR signaling has been mechanistically linked to the malignant behavior of several epithelial human tumors, including bladder cancer.…”

Molecular characterization of early-stage bladder carcinomas by expression profiles, FGFR3 mutation status, and loss of 9q

“…In recent years, genome-wide expression profiling by the use of microarray technology has contributed to extensive and new insights into the complex gene expression patterns and dysregulation of genes occurring in urothelial neoplasias (Thykjaer et al, 2001;Dyrskjt et al, 2003Dyrskjt et al, , 2004Dyrskjt et al, , 2005Mor et al, 2003;SanchezCarbayo et al, 2003;Modlich et al, 2004;Blaveri et al, 2005;Kim et al, 2005;Wild et al, 2005). Microarray analyses have not only delineated gene expression profiles distinct for different histological subtypes (Thykjaer et al, 2001;Dyrskjt et al, 2003Dyrskjt et al, , 2004Sanchez-Carbayo et al, 2003;Blaveri et al, 2005;Wild et al, 2005), but also gene expression signatures of importance for tumor recurrence and progression (Dyrskjt et al, 2003(Dyrskjt et al, , 2005Modlich et al, 2004;Wild et al, 2005), and patient survival (Blaveri et al, 2005;Kim et al, 2005).…”

“…Microarray analyses have not only delineated gene expression profiles distinct for different histological subtypes (Thykjaer et al, 2001;Dyrskjt et al, 2003Dyrskjt et al, , 2004Sanchez-Carbayo et al, 2003;Blaveri et al, 2005;Wild et al, 2005), but also gene expression signatures of importance for tumor recurrence and progression (Dyrskjt et al, 2003(Dyrskjt et al, , 2005Modlich et al, 2004;Wild et al, 2005), and patient survival (Blaveri et al, 2005;Kim et al, 2005). Whereas previous microarray studies of bladder cancer mostly have been dedicated to isolate gene expression profiles and predictors that classify tumors according to stage, recurrence and outcome, we focus on a comprehensive molecular characterization of Ta and T1 tumors.…”