Differential expression of SDF-1 isoforms in bladder cancer

Miguel Gosalbez, Marie C. Hupe, Soum D. Lokeshwar, Travis J. Yates, John Shields, Muthu K. Veerapen, Axel S. Merseburger, Charles J. Rosser, Mark S. Soloway, Vinata B. Lokeshwar

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10 Scopus citations

Abstract

Purpose 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. Materials and 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.

Original languageEnglish (US)
Pages (from-to)1899-1905
Number of pages7
JournalJournal of Urology
Volume191
Issue number6
DOIs
StatePublished - Jun 2014
Externally publishedYes

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Keywords

  • biological
  • chemokine CXCL12
  • local
  • neoplasm recurrence
  • prognosis
  • tumor markers
  • urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Gosalbez, M., Hupe, M. C., Lokeshwar, S. D., Yates, T. J., Shields, J., Veerapen, M. K., Merseburger, A. S., Rosser, C. J., Soloway, M. S., & Lokeshwar, V. B. (2014). Differential expression of SDF-1 isoforms in bladder cancer. Journal of Urology, 191(6), 1899-1905. https://doi.org/10.1016/j.juro.2013.11.053