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Background: Approximately 40% of males with low Gleasongrade clinically localized prostate cancer (PCa) at biopsy werefinally diagnosed with high Gleason grade PCa at radicalprostatectomy (RP). Therefore, a more reliable assessment ofthe Gleason grade prior to RP is required. Readily availablemodalities such as circulating biomarkers may be useful forthis purpose. The aim of this study was to evaluate the abilityof preoperative interleukin 6 (IL-6) and its soluble receptor(sIL-6R), as well as urokinase-type plasminogen activator (u-PA), its receptor (u-PAR) and the inhibitor (PAI-1) to predictGleason score upgrading. Patients and Methods: A total of 51PCa patients with biopsy Gleason score ≤7 were studied.Preoperative serum samples were collected prior to digitalrectal examination (DRE) and TRUS. Blood was collected intonon-heparinized tubes and serum was separated within 1 h ofblood collection. The serum was stored at –80˚C and thenthawed just prior to testing. Serum levels of PSA, free-PSA andIL-6 were measured using the Immulite 2000 automated assay(DPC, Los Angeles, CA, USA). The concentrations of sIL-6R(R&D Systems, Minneapolis, MN, USA), uPA, uPAR and PAI-1 (Assaypro, Winfield, MO, USA) in serum were determinedaccording to the manufacturer’s instructions using the ELISAtest. Every sample was run in duplicate and the mean was used.The differences between the two measurements were minimal.Results: GS upgrading was defined as a Gleason sum increasebetween biopsy and RP from ≤7 to >7, since this is importantfor the therapeutic strategy. On this basis, an upgrade was notedin 5 (10%) samples. Median sIL-6R values were found to besignificantly higher in patients with GS upgrading (differencein medians, 28.40 ng/ml; 95% CI, 5.60-49.44; p=0.024). Theassociation between sIL-6R and GS upgrading became moresignificant by using the sIL-6R/IL-6 ratio (difference inmedians, 7.77; 95% CI, 1.72-11.28; p=0.011). Sensitivity andspecificity of sIL-6R and the sIL-6R/IL-6 ratio were exploredby ROC curve analysis (Figure 1).Figure 1. ROC analysis comparing sIL-6R (--) and sIL-6R/IL-6 ratio(–).The results indicated an extremely good ability to predict theprobability of biopsy Gleason sum upgrading of the twoparameters (sIL-6R: AUC=0.80; 95% CI, 0.63-0.97; p=0.026.sIL-6R/IL-6 ratio: AUC=0.84; 95% CI, 0.69-0.98; p=0.014).The optimal cut-off point for sIL-6R was 76.5 ng/ml, providinga sensitivity of 80% and a specificity of 76%, whereas for thesIL-6R/IL-6 ratio the optimal cut-off point was 13.5 withcomparable sensitivity (80%), but higher specificity (83%).Discussion and Conclusion: sIL-6R may be a significantcirculating biomarker employed to predict GS upgrading inpatients with a biopsy GS ≤7. Moreover, this ability appears tobe enhanced by calculating the sIL-6R/IL-6 ratio. Thesefindings may provide an additional ‘staging tool’ for PCapatients, which may be of great significance in guidingclinicians’ treatment choices, according to current guidelines.1 Shariat SF, Andrews B, Kattan MW, Kim J, Wheeler TMand Slawin KM: Plasma levels of interleukin-6 and itssoluble receptor are associated with prostate cancerprogression and metastasis. Urology 58: 1008-1015, 2001.2 Spiotto MT and Chung TD: STAT3 mediates IL-6-inducedneuroendocrine differentiation in prostate cancer cells.Prostate 42: 186-195, 2000.3 Deeble PD, Murphy DJ, Parsons SJ and Cox ME:Interleukin-6-and cyclic AMP-mediated signaling potentiatesneuroendocrine differentiation of LNCaP prostate tumorcells. Mol Cell Biol 21: 84718482, 2001.
Lingua originaleEnglish
Numero di pagine1
Stato di pubblicazionePublished - 2012


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