Cancer Res Treat.  2015 Apr;47(2):306-312. 10.4143/crt.2014.015.

CCL2 Chemokine as a Potential Biomarker for Prostate Cancer: A Pilot Study

• Tsaur I
• Noack A
• Makarevic
• Oppermann
• Waaga-Gasser AM
• Gasser M
• Borgmann H
• Huesch T
• Gust KM
• Reiter M
• Schilling
• Bartsch G
• Haferkamp
• Blaheta RA

• KMID: 2132810
• DOI: http://doi.org/10.4143/crt.2014.015

Abstract

PURPOSE
Prostate specific antigen is not reliable in diagnosing prostate cancer (PCa), making the identification of novel, precise diagnostic biomarkers important. Since chemokines are associated with more aggressive disease and poor prognosis in diverse malignancies, we aimed to investigate the diagnostic relevance of chemokines in PCa.
MATERIALS AND METHODS
Preoperative and early postoperative serum samples were obtained from 39 consecutive PCa patients undergoing radical prostatectomy. Serum from 15 healthy volunteers served as controls. Concentrations of CXCL12, CXCL13, CX3CL1, CCL2, CCL5, and CCL20 were measured in serum by Luminex. The expression activity of CXCR3, CXCR4, CXCR5, CXCR7, CXCL12, CXCL13, CX3CR1, CXCL1, CCR2, CCR5, CCR6, CCR7, CCL2, and CCL5 mRNA was assessed in tumor and adjacent normal tissue of prostatectomy specimens by quantitative real-time polymerase chain reaction. The associations of these chemokines with clinical and histological parameters were tested.
RESULTS
The gene expression activity of CCL2 and CCR6 was significantly higher in tumor tissue compared to adjacent normal tissue. CCL2 was also significantly higher in the blood samples of PCa patients, compared to controls. CCL5, CCL20, and CX3CL1 were lower in patient serum, compared to controls. CCR2 tissue mRNA was negatively correlated with the Gleason score and grading.
CONCLUSION
Chemokines are significantly modified during tumorigenesis of PCa, and CCL2 is a promising diagnostic biomarker.

Keyword

Prostatic neoplasms; Diagnosis; Biological markers; Chemokines; Chemokine CCL2

MeSH Terms

Biological Markers
Carcinogenesis
Chemokine CCL2*
Chemokines
Diagnosis
Gene Expression
Healthy Volunteers
Humans
Neoplasm Grading
Passive Cutaneous Anaphylaxis
Pilot Projects*
Prognosis
Prostate-Specific Antigen
Prostatectomy
Prostatic Neoplasms*
Real-Time Polymerase Chain Reaction
RNA, Messenger
Biological Markers
Chemokine CCL2
Chemokines
Prostate-Specific Antigen
RNA, Messenger

Figure

• 

  Fig. 1. Analysis of chemokine gene activity obtained with real-time quantitative polymerase chain reaction in tumor tissue compared to normal adjacent tissue in patients with prostate cancer. Vertical line, Tukey confidence interval for Hodges-Lehmann estimator; ●, lower and upper limit of the Tukey confidence interval; ▲, Hodges-Lehmann estimator of the median fold difference.

• 

  Fig. 2. Results from Pearson’s regression test for chemokine expression in prostate cancer samples and tumor grade or Gleason score. Presented as regression line (thick) and confidence borders (thin lines) with confidence p=0.95. p, p-value of the regression test; B, regression coefficient; r, Pearson’s correlation coefficient. Chemokine expression as fold difference obtained with real-time quantitative polymerase chain reaction.

• 

  Fig. 3. Chemokine concentration obtained with Luminex. Chemokines with significant differences between at least two samples are presented. Box-plot: Con, control serum; Pre, preoperative serum; Post, postoperative serum. Box: lower line, quartile Q1 (25%-quantile); middle line, median; upper line, Q3 (75%-quantile); aerials, extreme values; horizontal bracket, respective p-value of the concentration difference in Wilcoxon-matched-pairs or Wilcoxon-Mann-Whitney test.

Reference

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