Differential Expression of SDF-1 Isoforms in Bladder Cancer

    Authors

    M. Gosalbez; M. C. Hupe; S. D. Lokeshwar; T. J. Yates; J. Shields; M. K. Veerapen; A. S. Merseburger; C. J. Rosser; M. S. Soloway;V. B. Lokeshwar

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    Abbreviated Journal Title

    J. Urol.

    Keywords

    urinary bladder neoplasms; chemokine CXCL12; tumor markers, biological; prognosis; neoplasm recurrence, local; CELL CARCINOMA; BREAST-CANCER; CHEMOKINE; RECEPTOR; CXCL12; CXCR7; PROGRESSION; SURVIVAL; DISEASE; AXIS; Urology & Nephrology

    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 (alpha, beta and gamma) in bladder cancer. Materials and Methods: Using quantitative polymerase chain reaction we measured SDF-1 alpha, beta and gamma 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-1 beta mRNA was significantly over expressed 2.5-fold to sixfold in bladder cancer compared to normal bladder tissues. SDF-1 alpha was expressed in bladder tissues but SDF-1 gamma was undetectable. On multivariate analysis SDF-1 beta was an independent predictor of metastasis and disease specific mortality (p = 0.017 and 0.043, respectively). In exfoliated urothelial cells only SDF-1 beta 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-1 beta 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-1 beta mRNA levels in bladder cancer tissues predict a poor prognosis. Furthermore, SDF-1 beta mRNA levels in exfoliated cells detect bladder cancer with high sensitivity and they are a potential predictor of future recurrence.

    Journal Title

    Journal of Urology

    Volume

    191

    Issue/Number

    6

    Publication Date

    1-1-2014

    Document Type

    Article

    Language

    English

    First Page

    1899

    Last Page

    1905

    WOS Identifier

    WOS:000336531100102

    ISSN

    0022-5347

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