title: Expression of Engrailed-2 (EN2) protein in bladder cancer and its potential utility as a urinary diagnostic biomarker.
abstract: Despite significant advances in our understanding of the molecular pathology of bladder cancer, it remains a significant health problem with high morbidity and mortality associated with muscle-invasive bladder cancer (stages T2+), and high costs associated with the surveillance of non-muscle-invasive bladder cancer (NMIBC, stages Ta/T1/Tis). Moreover, current diagnostic biomarkers are suboptimal and of poor utility for low grade disease and surveillance. In this study, we show that the Engrailed-2 (EN2) transcription factor is expressed in, and secreted by, bladder cancer cell lines and patient tumour specimens, justifying an evaluation of urinary EN2 as a diagnostic biomarker in bladder cancer using archived samples from an established biospecimen collection. In patients with NMIBC, urinary EN2 was detected in most cases with an overall sensitivity of 82% and specificity of 75%. The sensitivity for stage Ta and T1 tumours was 71% and 76%, respectively, and 94% for stage T2+ tumours. This compares favourably with existing markers. The sensitivity for tumour grades 1, 2 and 3 was 69%, 78% and 87%, respectively. Thus urinary EN2 has the potential to be a more sensitive and specific protein biomarker for NMIBC than currently available tests.
authors: Oncology, Faculty of Health and Medical Sciences, Leggett Building, University of Surrey, Surrey GU2 7WG, UK. Electronic address: r.morgan@surrey.ac.uk.
authors: Richard
authors: R
authors: Morgan
authors: School of Cancer Sciences, University of Birmingham, West Midlands B15 2TT, UK.
authors: Richard T
authors: RT
authors: Bryan
authors: Oncology, Faculty of Health and Medical Sciences, Leggett Building, University of Surrey, Surrey GU2 7WG, UK.
authors: Saqib
authors: S
authors: Javed
authors: Oncology, Faculty of Health and Medical Sciences, Leggett Building, University of Surrey, Surrey GU2 7WG, UK.
authors: Francesca
authors: F
authors: Launchbury
authors: Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, West Midlands B15 2TT, UK.
authors: Maurice P
authors: MP
authors: Zeegers
authors: Department of Public Health, Epidemiology and Biostatistics, University of Birmingham, West Midlands B15 2TT, UK.
authors: K K
authors: KK
authors: Cheng
authors: School of Cancer Sciences, University of Birmingham, West Midlands B15 2TT, UK.
authors: Nicholas D
authors: ND
authors: James
authors: School of Cancer Sciences, University of Birmingham, West Midlands B15 2TT, UK.
authors: D Michael A
authors: DM
authors: Wallace
authors: Cancer Research UK Centre, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, West Yorkshire LS9 7TF, UK.
authors: Carolyn D
authors: CD
authors: Hurst
authors: School of Cancer Sciences, University of Birmingham, West Midlands B15 2TT, UK.
authors: Douglas G
authors: DG
authors: Ward
authors: Cancer Research UK Centre, Leeds Institute of Molecular Medicine, St James's University Hospital, Leeds, West Yorkshire LS9 7TF, UK.
authors: Margaret A
authors: MA
authors: Knowles
authors: Oncology, Faculty of Health and Medical Sciences, Leggett Building, University of Surrey, Surrey GU2 7WG, UK.
authors: Hardev
authors: H
authors: Pandha
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D045744:Cell Line, Tumor; D018398:Homeodomain Proteins / Q000652:urine*; D006801:Humans; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000652:urine*; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*; D000099266:Engrailed 2 Protein
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; D000099266:Engrailed 2 Protein