title: Integrative functional genetic-epigenetic approach for selecting genes as urine biomarkers for bladder cancer diagnosis.
abstract: Early screening for bladder cancer (BC) holds the key to combat and control the increasing global burden of BC mortality. We presented a simple approach to characterize, analyze, and validate a panel of biomarkers in BC and their relationship to bilharziasis. We investigated voided urine and blood samples from patients with bladder cancer (n = 94), benign bladder lesions (n = 60), and age-matched normal controls (n = 56). This study was divided into the following phases. (1) We analyzed the expression of urinary Hyaluronoglucosaminidase 1 (HYAL1) protein in BC and control samples by zymography. (2) We performed bioinformatics analysis to retrieve a set of epigenetic regulators of HYAL1. (3) This set of three selected genes [long non-coding RNA-urothelial cancer associated 1(lncRNA-UCA1), microRNA-210, and microRNA-96] was then analyzed in the same urine samples used in phase I by quantitative real-time PCR. (4) A high reproducibility of gene selection results was also determined from statistical validation. The urinary expression of HYAL1 protein and its epigenetic regulators were higher in BC patients (P < .001). The receiver-operating characteristic curve analyses demonstrated that each one had good sensitivity and specificity for distinguishing BC patients from non-BC ones (HYAL1, 89.4 and 91.2 %; miR-210, 76.6 and 93 %; miR-96, 76.6 and 89.4 %; and lncRNA-UCA1, 91.5 and 96.5 %). There was a significant positive correlation between HYAL1 and the selected epigenetic biomarkers. The performance of this urine biomarker panel reached 100 % sensitivity and 89.5 % specificity for bladder cancer diagnosis.
authors.affiliation: Oncology Diagnostic Unit, Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, P.O. box 11381, Abbassia, Cairo, Egypt. Dr_sanaa_eissa@yahoo.com.
authors.forename: Sanaa
authors.initials: S
authors.lastname: Eissa
authors.affiliation: Oncology Diagnostic Unit, Medical Biochemistry and Molecular biology Department, Faculty of Medicine, Ain Shams University, P.O. box 11381, Abbassia, Cairo, Egypt.
authors.forename: Marwa
authors.initials: M
authors.lastname: Matboli
authors.affiliation: Pharmacogenetics and Stratified Medicine, University College London, London, UK.
authors.forename: Nada O E
authors.initials: NO
authors.lastname: Essawy
authors.affiliation: Urology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Youssef M
authors.initials: YM
authors.lastname: Kotb
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D044127:Epigenesis, Genetic / Q000235:genetics; D005260:Female; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000652:urine*; D008297:Male; D035683:MicroRNAs / Q000652:urine*; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000652:urine*; D012552:Schistosomiasis / Q000473:pathology / Q000652:urine; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; C543800:MIRN210 microRNA, human; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C515159:UCA1 RNA, human; D006821:Hyaluronoglucosaminidase
keywords: Bilharziasis; Bladder cancer; Hyaluronoglucosaminidase 1; Long non-coding RNA-UCA1; Urinary biomarkers; Urine cytology; miRNA