Tumor necrosis factor-related apoptosis inducing ligand-R4 decoy receptor expression is correlated with high Gleason scores, prostate-specific antigen recurrence, and decreased survival in patients with prostate carcinoma

Koksal, Ismail T.; Sanlioglu, Ahter D.; Karacay, Bahri; Griffith, Thomas S.; Sanlioglu, Salih

doi:10.1016/j.urolonc.2007.01.022

« Previous Next »Urologic Oncology: Seminars and Original Investigations
Volume 26, Issue 2 , Pages 158-165, March 2008

Tumor necrosis factor-related apoptosis inducing ligand-R4 decoy receptor expression is correlated with high Gleason scores, prostate-specific antigen recurrence, and decreased survival in patients with prostate carcinoma☆

Ismail T. Koksal, M.D.
- Human Gene Therapy Unit and the Department of Medical Biology and Genetics, Akdeniz University, Faculty of Medicine, Antalya, Turkey
- Department of Urology, Akdeniz University, Faculty of Medicine, Antalya, Turkey
Ahter D. Sanlioglu, Ph.D.
- Human Gene Therapy Unit and the Department of Medical Biology and Genetics, Akdeniz University, Faculty of Medicine, Antalya, Turkey
Bahri Karacay, Ph.D.
- Departments of Pediatrics-Urology and the Center for Gene Therapy at the University of Iowa, Iowa City 52242, IA, USA
Thomas S. Griffith, Ph.D.
- Departments of Pediatrics-Urology and the Center for Gene Therapy at the University of Iowa, Iowa City 52242, IA, USA
Salih Sanlioglu, V.M.D., Ph.D.
- Human Gene Therapy Unit and the Department of Medical Biology and Genetics, Akdeniz University, Faculty of Medicine, Antalya, Turkey
- Corresponding author. Tel.: +90-242-249-6157; fax: +90-242-227-4482.

Received 17 October 2006; received in revised form 16 January 2007; accepted 18 January 2007. published online 16 November 2007.

Abstract

Objective

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has recently been investigated because of its ability to selectively kill cancer cells. Despite recent publications mainly focusing on TRAIL resistance in cancer cells, little is known about how TRAIL contributes to the carcinogenesis process. Because the expression patterns of TRAIL and its receptors in patients with prostate carcinoma have recently been reported, this study investigated the significance of TRAIL and TRAIL receptor expression in connection to serum prostate-specific antigen (PSA) and Gleason scoring.

Materials and methods

A total of 98 patients were included in the study. Gleason scores, PSA, TRAIL, and TRAIL receptor expressions were used for the comparison purposes. The Spearman rho correlation test was administered to reveal the correlations among the variants. The Kruskal Wallis-Mann Whitney U or Friedman-Wilcoxon signed ranks test determined the statistical significance between the pairs. Multinomial and/or multiple binary logistic regression analyses were deployed to test whether TRAIL markers were independent variables to predict the prognosis of prostate cancer. Kaplan-Meier and log-rank tests were used to determine the survival rates.

Results

High-serum PSA levels were correlated with higher levels of TRAIL and TRAIL receptor expressions. Patients with high Gleason scores had higher levels of TRAIL-R4 decoy receptor expression but lower levels of TRAIL death ligand expression.

Conclusions

TRAIL-R4 decoy receptor expression is strongly correlated with PSA recurrence, which is suggestive of poor prognosis. High levels of TRAIL-R4 expression but low levels of TRAIL death ligand expression are connected to decreased survival.

Keywords: Tumor necrosis factor-related apoptosis inducing ligand, Gleason scoring, Prostate-specific antigen recurrence, Prostate cancer