title: Direct quantitative detection for cell-free miR-155 in urine: a potential role in diagnosis and prognosis for non-muscle invasive bladder cancer.
abstract: High recurrence rates of non-muscle invasive bladder cancer (NMIBC) in patients require lifelong testing and monitoring. The aim of this study is to develop a simplified RT-qPCR method (RT-qPCR-D) which directly quantifies cell-free miR-155 in urine without RNA extraction, and assess it as a potential tool in NMIBC detection. A pilot study including 60 urine samples was used to investigate the feasibility of RT-qPCR-D in detecting cell-free miR-155. Then, miR-155 levels were quantified in a large independent cohort of urine from 162 NIMBC patients, 76 cystitis patients, and 86 healthy donors using the RT-qPCR-D method. Changes of cell-free miR-155 before and after operation were also analyzed in 32 NIMBC patients. In pilot study, we found a significant linear association between RT-qPCR and RT-qPCR-D in urinary miR-155 detection. Both methods showed cell-free miR-155 were significantly increased in NMIBC patients, and could reflect their expression in tissues. Then, the increased expression of cell-free miR-155 was successfully validated in 162 NIMBC patients when compared with cystitis patients and healthy donors. Moreover, it distinguished NMIBC patients from others with 80.2% sensitivity and 84.6% specificity, which was superior to urine cytology. Cell-free miR-155 correlated with NMIBC stage and grade, and was an independent factor for predicting recurrence and progression to muscle invasion. In addition, cell-free miR-155 was significantly decreased after NMIBC patients underwent transurethral bladder resection. In conclusion, detection of cell-free miR-155 in urine using RT-qPCR-D is a simple and noninvasive approach which may be used for NMIBC diagnosis and prognosis prediction.
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Traffic Hospital of Shandong Province, Jinan 250031, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Traffic Hospital of Shandong Province, Jinan 250031, China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, Traffic Hospital of Shandong Province, Jinan 250031, China.
authors.forename: Aiju
authors.initials: A
authors.lastname: Fang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Lutao
authors.initials: L
authors.lastname: Du
authors.affiliation: Department of Clinical Laboratory, Qilu Hospital, Shandong University, Jinan 250012, China.
authors.forename: Chuanxin
authors.initials: C
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D003556:Cystitis / Q000652:urine; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000652:urine*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000473:pathology / Q000652:urine*; D010865:Pilot Projects; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D001743:Urinary Bladder / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor; C524942:MIRN155 microRNA, human; D035683:MicroRNAs
keywords: biomarker; cell-free; miR-155; non-muscle invasive bladder cancer; urine