title: Differential expression of SDF-1 isoforms in bladder cancer.
abstract: OBJECTIVE
  SDF-1 is a ligand of the chemokine receptors CXCR4 and 7. The 6 known SDF-1 isoforms are generated by alternative mRNA splicing. While SDF-1 expression has been detected in various malignancies, only few groups have reported differential expression of SDF-1 isoforms and its clinical significance. We evaluated the expression of 3 SDF-1 isoforms (α, β and γ) in bladder cancer.
  
  
  METHODS
  Using quantitative polymerase chain reaction we measured SDF-1α, β and γ mRNA levels in 25 normal and 44 bladder cancer tissues, and in 210 urine specimens (28 normal, 74 benign, 57 bladder cancer, 35 bladder cancer history, 8 other cancer history and 8 other cancer) from consecutive patients. Levels were correlated with clinical outcome.
  
  
  RESULTS
  Of the SDF-1 isoforms only SDF-1β mRNA was significantly over expressed 2.5-fold to sixfold in bladder cancer compared to normal bladder tissues. SDF-1α was expressed in bladder tissues but SDF-1γ was undetectable. On multivariate analysis SDF-1β was an independent predictor of metastasis and disease specific mortality (p=0.017 and 0.043, respectively). In exfoliated urothelial cells only SDF-1β mRNA levels were differentially expressed with 91.2% sensitivity and 73.8% specificity for detecting bladder cancer. In patients with a bladder cancer history increased SDF-1β levels indicated a 4.3-fold increased risk of recurrence within 6 months (p=0.0001).
  
  
  CONCLUSIONS
  SDF-1 isoforms are differentially expressed in bladder tissues and exfoliated urothelial cells. SDF-1β mRNA levels in bladder cancer tissues predict a poor prognosis. Furthermore, SDF-1β mRNA levels in exfoliated cells detect bladder cancer with high sensitivity and they are a potential predictor of future recurrence.
authors.affiliation: Department of Urology University of Miami - Miller School of Medicine, Miami, Florida, 33101.
authors.forename: Miguel
authors.initials: M
authors.lastname: Gosalbez
authors.affiliation: Department of Urology University of Miami - Miller School of Medicine, Miami, Florida, 33101.|Department of Urology and Urologic Oncology Hannover Medical School (MHH), Hannover Germany.
authors.forename: Marie C
authors.initials: MC
authors.lastname: Hupe
authors.affiliation: Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, Florida, 33101.
authors.forename: Soum D
authors.initials: SD
authors.lastname: Lokeshwar
authors.affiliation: Department of Urology University of Miami - Miller School of Medicine, Miami, Florida, 33101.
authors.forename: Travis J
authors.initials: TJ
authors.lastname: Yates
authors.affiliation: Department of Urology University of Miami - Miller School of Medicine, Miami, Florida, 33101.
authors.forename: John
authors.initials: J
authors.lastname: Shields
authors.affiliation: Department of Human Genetics and Hussman Institute of Human Genetics, University of Miami - Miller School of Medicine, Miami, Florida 33136.
authors.forename: Muthu K
authors.initials: MK
authors.lastname: Veerapen
authors.affiliation: Department of Urology and Urologic Oncology Hannover Medical School (MHH), Hannover Germany.
authors.forename: Axel S
authors.initials: AS
authors.lastname: Merseburger
authors.affiliation: University of Central Florida College of Medicine, Orlando, Florida.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Rosser
authors.affiliation: Department of Urology University of Miami - Miller School of Medicine, Miami, Florida, 33101.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Soloway
authors.affiliation: Department of Urology University of Miami - Miller School of Medicine, Miami, Florida, 33101.|Sylvester Comprehensive Cancer Center, University of Miami - Miller School of Medicine, Miami, Florida, 33101.
authors.forename: Vinata B
authors.initials: VB
authors.lastname: Lokeshwar
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D054377:Chemokine CXCL12 / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D020033:Protein Isoforms; D012334:RNA, Neoplasm
keywords: biological; chemokine CXCL12; local; neoplasm recurrence; prognosis; tumor markers; urinary bladder neoplasms