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

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 - Jan 1 2014
Externally publishedYes

Fingerprint

Urinary Bladder Neoplasms
Protein Isoforms
Messenger RNA
Urinary Bladder
Recurrence
Neoplasms
Chemokine Receptors
Alternative Splicing
Multivariate Analysis
Urine
Neoplasm Metastasis
Ligands
Sensitivity and Specificity
Polymerase Chain Reaction
Mortality

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., ... 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

Differential expression of SDF-1 isoforms in bladder cancer. / Gosalbez, Miguel; Hupe, Marie C.; Lokeshwar, Soum D.; Yates, Travis J.; Shields, John; Veerapen, Muthu K.; Merseburger, Axel S.; Rosser, Charles J.; Soloway, Mark S.; Lokeshwar, Vinata B.

In: Journal of Urology, Vol. 191, No. 6, 01.01.2014, p. 1899-1905.

Research output: Contribution to journalArticle

Gosalbez, M, Hupe, MC, Lokeshwar, SD, Yates, TJ, Shields, J, Veerapen, MK, Merseburger, AS, Rosser, CJ, Soloway, MS & Lokeshwar, VB 2014, 'Differential expression of SDF-1 isoforms in bladder cancer', Journal of Urology, vol. 191, no. 6, pp. 1899-1905. https://doi.org/10.1016/j.juro.2013.11.053
Gosalbez M, Hupe MC, Lokeshwar SD, Yates TJ, Shields J, Veerapen MK et al. Differential expression of SDF-1 isoforms in bladder cancer. Journal of Urology. 2014 Jan 1;191(6):1899-1905. https://doi.org/10.1016/j.juro.2013.11.053
Gosalbez, Miguel ; Hupe, Marie C. ; Lokeshwar, Soum D. ; Yates, Travis J. ; Shields, John ; Veerapen, Muthu K. ; Merseburger, Axel S. ; Rosser, Charles J. ; Soloway, Mark S. ; Lokeshwar, Vinata B. / Differential expression of SDF-1 isoforms in bladder cancer. In: Journal of Urology. 2014 ; Vol. 191, No. 6. pp. 1899-1905.
@article{e24bb31b79ab481cbfe3ac086b52b965,
title = "Differential expression of SDF-1 isoforms in bladder cancer",
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.",
keywords = "biological, chemokine CXCL12, local, neoplasm recurrence, prognosis, tumor markers, urinary bladder neoplasms",
author = "Miguel Gosalbez and Hupe, {Marie C.} and Lokeshwar, {Soum D.} and Yates, {Travis J.} and John Shields and Veerapen, {Muthu K.} and Merseburger, {Axel S.} and Rosser, {Charles J.} and Soloway, {Mark S.} and Lokeshwar, {Vinata B}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.juro.2013.11.053",
language = "English (US)",
volume = "191",
pages = "1899--1905",
journal = "Journal of Urology",
issn = "0022-5347",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Differential expression of SDF-1 isoforms in bladder cancer

AU - Gosalbez, Miguel

AU - Hupe, Marie C.

AU - Lokeshwar, Soum D.

AU - Yates, Travis J.

AU - Shields, John

AU - Veerapen, Muthu K.

AU - Merseburger, Axel S.

AU - Rosser, Charles J.

AU - Soloway, Mark S.

AU - Lokeshwar, Vinata B

PY - 2014/1/1

Y1 - 2014/1/1

N2 - 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.

AB - 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.

KW - biological

KW - chemokine CXCL12

KW - local

KW - neoplasm recurrence

KW - prognosis

KW - tumor markers

KW - urinary bladder neoplasms

UR - http://www.scopus.com/inward/record.url?scp=84900399034&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84900399034&partnerID=8YFLogxK

U2 - 10.1016/j.juro.2013.11.053

DO - 10.1016/j.juro.2013.11.053

M3 - Article

C2 - 24291546

AN - SCOPUS:84900399034

VL - 191

SP - 1899

EP - 1905

JO - Journal of Urology

JF - Journal of Urology

SN - 0022-5347

IS - 6

ER -