Gene expression profiling in bladder cancer to identify potential therapeutic targets



Hussain, Syed A, Palmer, Daniel H ORCID: 0000-0002-7147-5703, Syn, Wing Kin, Sacco, Joseph J, Lloyd, Bryony, Jithesh, Puthen, Arrand, John R, Barton, Darren, Ansari, Jawaher, Sibson, David R
et al (show 1 more authors) (2013) Gene expression profiling in bladder cancer to identify potential therapeutic targets. JOURNAL OF CLINICAL ONCOLOGY, 31 (15). pp. 1147-1159.

Access the full-text of this item by clicking on the Open Access link.

Abstract

Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation.

Item Type: Article
Uncontrolled Keywords: Urothelium, Humans, Carcinoma, Biopsy, Cystoscopy, Microarray Analysis, Immunohistochemistry, Cluster Analysis, Gene Expression Profiling, Signal Transduction, Cell Cycle, Cell Proliferation, Complement Pathway, Classical, Down-Regulation, Gene Expression Regulation, Neoplastic, Up-Regulation, Aged, Aged, 80 and over, Middle Aged, Female, Male, Urinary Bladder Neoplasms, Osteopontin, Molecular Targeted Therapy, Neoplasm Grading, Transcriptome
Depositing User: Symplectic Admin
Date Deposited: 19 Jan 2018 10:50
Last Modified: 19 Jan 2023 06:43
DOI: 10.3892/ijo.2017.3893
Open Access URL: https://www.spandidos-publications.com/ijo/50/4/11...
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3016433