Gene expression profiling in bladder cancer identifies potential therapeutic targets

Research output: Contribution to journalArticlepeer-review

Authors

  • Syed A Hussain
  • Daniel H Palmer
  • Wing-Kin Syn
  • Joseph J Sacco
  • Richard M D Greensmith
  • Taha Elmetwali
  • Vijay Aachi
  • Bryony H Lloyd
  • Puthen V Jithesh
  • Darren Barton
  • Jawaher Ansari
  • D Ross Sibson

External organisations

  • Department of Molecular and Clinical Cancer Medicine, University of Liverpool and Clatterbridge Cancer Centre NHS Foundation Trust, Sherrington Building, Ashton Street, Liverpool, Merseyside L69 3GA, UK.
  • Regeneration and Repair Group, The Institute of Hepatology, Foundation of Liver Research, London SE5 9NT, UK.
  • The Royal Liverpool and Broadgreen University Hospital Trust, Liverpool L7 8XP, UK.
  • University of Birmingham
  • Beatson West Scotland Cancer Centre, Glasgow G12 0YN, UK.

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.

Details

Original languageEnglish
Pages (from-to)1147-1159
Number of pages13
JournalInternational Journal of Oncology
Volume50
Issue number4
Early online date2 Mar 2017
Publication statusPublished - Apr 2017