Gene profiling suggests a common evolution of bladder cancer subtypes

Abstract

BackgroundBladder cancer exists as several distinct subtypes, including urothelial carcinoma (UCa), squamous cell carcinoma (SCCa), adenocarcinoma and small cell carcinoma. These entities, despite showing distinct morphology and clinical behavior, arise from the urothelial lining and are often accompanied by similar precursor/in situ findings. The relationship between these subtypes has not been explored in detail.MethodsWe compared gene expression analysis of the two most common subtypes of bladder cancer, UCa (n = 10) and SCCa (n = 9), with an additional comparison to normal urothelium from non-cancer patients (n = 8) using Affymetrix GeneChip Human genome arrays (Affymetrix, Santa Clara, CA). The results were stratified by supervised and unsupervised clustering analysis, as well as by overall fold change in gene expression.ResultsWhen compared to normal urothelium, UCa showed differential expression of 155 genes using a 5-fold cut-off. Examples of differentially regulated genes included topoisomerases, cancer-related transcription factors and cell cycle mediators. A second comparison of normal urothelium to SCCa showed differential expression of 503 genes, many of which were related to squamous-specific morphology (desmosomal complex, intermediate filaments present within squamous epithelium, squamous cornifying proteins, and molecules upregulated in squamous carcinomas from other anatomic sites). When compared, 137 genes were commonly dysregulated in both UCa and SCCa as compared to normal urothelium. All dysregulated genes in UCa were shared in common with SCCa, with the exception of only 18 genes. Supervised clustering analysis yielded correct classification of lesions in 26/27 (96%) of cases and unsupervised clustering analysis yielded correct classification in 25/27 (92.6%) of cases.ConclusionsThe results from this analysis suggest that bladder SCCa shares a significant number of gene expression changes with conventional UCa, but also demonstrates an additional set of alterations that is unique to this entity that defines the squamous phenotype. The similarity in deregulated gene products suggests that SCCa may be a much more closely related entity at the molecular level to conventional UCa than previously hypothesized.

Enrichment of genes associated with squamous differentiation in cancer initiating cells isolated from urothelial cells transformed by the environmental toxicant arsenite

“…A previous study explored the relationship between UCCs and squamous cell carcinomas (SCCa) of the bladder and showed UCCs to express very few unique dysregulated genes and share the majority of its dysregulated genes relative to normal urothelium with SSCa (Hansel et al 2013). In contrast, SCCa, while expressing many genes common with UCCs, express many more dysregulated genes common in SCCa arising at other sites.…”

The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part B: Prostate and Bladder Tumours

“…Squamous cell carcinoma is defined by the presence of intercellular bridges or keratinization and may be present in up to 40% of invasive urothelial carcinomas [63][64][65][66]. It is almost never associated with human papillomavirus infection, with the rare exception of some cases with a basaloid morphology [67,68].…”

Identification of differentially expressed genes and signaling pathways in ovarian cancer by integrated bioinformatics analysis

“…Many studies have shown that the protein expression of the ADH1B gene is downregulated in many tumors. 47 , 48 Compared with levels in normal tissues, the mRNA levels of ADH1B in colorectal cancer tissues were low. 49 The risk of residual lesions in patients with high-grade ovarian cancer after cytoreductive surgery is closely related to the high expression of ADH1B.…”