title: Gene expression profiling in bladder cancer identifies potential therapeutic targets.
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.
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Syed A
authors.initials: SA
authors.lastname: Hussain
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Palmer
authors.affiliation: Regeneration and Repair Group, The Institute of Hepatology, Foundation of Liver Research, London SE5 9NT, UK.
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Syn
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Sacco
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Richard M D
authors.initials: RMD
authors.lastname: Greensmith
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Taha
authors.initials: T
authors.lastname: Elmetwali
authors.affiliation: The Royal Liverpool and Broadgreen University Hospital Trust, Liverpool L7 8XP, UK.
authors.forename: Vijay
authors.initials: V
authors.lastname: Aachi
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Bryony H
authors.initials: BH
authors.lastname: Lloyd
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: Puthen V
authors.initials: PV
authors.lastname: Jithesh
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: John
authors.initials: J
authors.lastname: Arrand
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Darren
authors.initials: D
authors.lastname: Barton
authors.affiliation: Beatson West Scotland Cancer Centre, Glasgow G12 0YN, UK.
authors.forename: Jawaher
authors.initials: J
authors.lastname: Ansari
authors.affiliation: Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool L69 3GA, UK.
authors.forename: D Ross
authors.initials: DR
authors.lastname: Sibson
authors.affiliation: School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: Nicholas D
authors.initials: ND
authors.lastname: James
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle; D049109:Cell Proliferation; D016000:Cluster Analysis; D003171:Complement Pathway, Classical / Q000235:genetics; D003558:Cystoscopy; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D053495:Osteopontin / Q000378:metabolism*; D015398:Signal Transduction; D059467:Transcriptome; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000473:pathology
chemical_list: C506895:SPP1 protein, human; D053495:Osteopontin