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P050 Cxcr4 inhibition reduces bone metastases by affecting tumour growth and tumorigenic potential in prostate cancer preclinical models
A B S T R A C T S / E U R O P E A N U R O L O G Y S U P P L E M E N T S 13 (2014) 103—194
and 25 patients with BC. Most of the patients with PC were CTC positive. These patients had elevated levels of MMP9 (238±71 ng/ml) and VEGF (209±161 pg/ml). The highest level of MMP2 (266±68 ng/ml) was in the CTC borderline group. On the other hand the majority of BC patients were CTC negative. These patients had elevated level of MMP9 (332±228 ng/ml). CTC positive patients had elevated levels of MMP2 (346±64 ng/ml) and VEGF (464±294 pg/ml). Conclusions: Our preliminary results may be influenced by the small numbers of patients but they indicate a possible correlation between the presence of CTCs and the serum marker levels of metastatic process. The levels of serum markers are higher in breast cancer patients despite the fact that most of them are CTC negative. An important goal is to increase the number of patients for statistical evaluation. We will continue collecting the results and we will evaluate the clinical outcome of the patients as well. This work was supported by grants SVV 266 515, GAUK 539512 and IGA MZ NT 12205-5. P049 Assessment of association between genetic variant in hsa-miR-146a gene and prostate cancer risk in Serbian population Z. Nikolic 1 , D. Savic Pavicevic 1 , N. Vucic 1 , V. Vukotic 2 , S. Tomovic 3 , S. Cerovic 4 , N. Filipovic 2 , S. Romac 1 , G. Brajuskovic 1 . 1 Faculty of Biology, University of Belgrade, Dept. of Biochemistry and Molecular Biology, Belgrade, Serbia; 2 Clinical Centre Dr Dragiša Mišovi´c, Dept. of Urology, Belgrade, Serbia; 3 Urological Center Urologija Vuk, Dept. of Urology, Belgrade, Serbia; 4 Military Medical Academy, Dept. of Pathology, Belgrade, Serbia Introduction & Objectives: Prostate cancer (PCa) is the most common cancer and the third leading cause of cancer-related deaths among males in developed countries. In Serbian population, data for the period 1999–2009 suggest increasing trend of newly diagnosed PCa cases and PCa-related mortality. Alarming PCa statistics has led to focusing research efforts on discovering molecular mechanisms underlying its onset and progression. Several lines of evidence implicated non-coding RNA (ncRNA) in malignant transformation process. A SNP located in has-miR-146a has been analyzed for association with various cancers, including PCa. Two previous studies have provided inconsistent results regarding association between SNP (rs2910164) in hsa-miR-146a gene and PCa risk. The possible association between rs2910164 and PCa onset or progression to the more aggressive form has not been assessed in a population of European descent. Material & Methods: In this study, 286 samples of peripheral blood were obtained from the patients with PCa and 271 samples from patients with benign prostatic hyperplasia (BPH). 199 volunteers derived from general population who gave samples of buccal swabs comprised the control group. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotyping of rs2910164 was performed using Taqman® SNP Genotyping Assay. Analysis of SNP association was done using PLINK and SNPStats software. Results: The comparison of genotype frequencies in PCa patients and controls yielded no evidence of association between rs2910164 and the risk of PCa. Eventhough rs2910164 showed no association with PCa risk, heterozygous genotype was found to be associated with higher GS, as well as with the presence of distant metastases. The analysis of association between rs2910164 and the serum PSA level at diagnosis has shown statistically significant difference in genotype distribution among subgroups of patients with high (PSA>20 ng/ml) and low PSA (PSAGC = 2.22, 95% CI 1.24–3.97; ORCC = 0.47, 95% CI 0.13–1.68). When comparing genotype distributions among PCa and BPH patients, no statistically significant difference was found. Nevertheless, for log-additive model of inheritance, statistical
127
trend of significance (0.05
and 25 patients with BC. Most of the patients with PC were CTC positive. These patients had elevated levels of MMP9 (238±71 ng/ml) and VEGF (209±161 pg/ml). The highest level of MMP2 (266±68 ng/ml) was in the CTC borderline group. On the other hand the majority of BC patients were CTC negative. These patients had elevated level of MMP9 (332±228 ng/ml). CTC positive patients had elevated levels of MMP2 (346±64 ng/ml) and VEGF (464±294 pg/ml). Conclusions: Our preliminary results may be influenced by the small numbers of patients but they indicate a possible correlation between the presence of CTCs and the serum marker levels of metastatic process. The levels of serum markers are higher in breast cancer patients despite the fact that most of them are CTC negative. An important goal is to increase the number of patients for statistical evaluation. We will continue collecting the results and we will evaluate the clinical outcome of the patients as well. This work was supported by grants SVV 266 515, GAUK 539512 and IGA MZ NT 12205-5. P049 Assessment of association between genetic variant in hsa-miR-146a gene and prostate cancer risk in Serbian population Z. Nikolic 1 , D. Savic Pavicevic 1 , N. Vucic 1 , V. Vukotic 2 , S. Tomovic 3 , S. Cerovic 4 , N. Filipovic 2 , S. Romac 1 , G. Brajuskovic 1 . 1 Faculty of Biology, University of Belgrade, Dept. of Biochemistry and Molecular Biology, Belgrade, Serbia; 2 Clinical Centre Dr Dragiša Mišovi´c, Dept. of Urology, Belgrade, Serbia; 3 Urological Center Urologija Vuk, Dept. of Urology, Belgrade, Serbia; 4 Military Medical Academy, Dept. of Pathology, Belgrade, Serbia Introduction & Objectives: Prostate cancer (PCa) is the most common cancer and the third leading cause of cancer-related deaths among males in developed countries. In Serbian population, data for the period 1999–2009 suggest increasing trend of newly diagnosed PCa cases and PCa-related mortality. Alarming PCa statistics has led to focusing research efforts on discovering molecular mechanisms underlying its onset and progression. Several lines of evidence implicated non-coding RNA (ncRNA) in malignant transformation process. A SNP located in has-miR-146a has been analyzed for association with various cancers, including PCa. Two previous studies have provided inconsistent results regarding association between SNP (rs2910164) in hsa-miR-146a gene and PCa risk. The possible association between rs2910164 and PCa onset or progression to the more aggressive form has not been assessed in a population of European descent. Material & Methods: In this study, 286 samples of peripheral blood were obtained from the patients with PCa and 271 samples from patients with benign prostatic hyperplasia (BPH). 199 volunteers derived from general population who gave samples of buccal swabs comprised the control group. For individuals diagnosed with PCa clinicopathological characteristics including serum prostate-specific antigen level at diagnosis, Gleason score (GS) and clinical stage were determined. Genotyping of rs2910164 was performed using Taqman® SNP Genotyping Assay. Analysis of SNP association was done using PLINK and SNPStats software. Results: The comparison of genotype frequencies in PCa patients and controls yielded no evidence of association between rs2910164 and the risk of PCa. Eventhough rs2910164 showed no association with PCa risk, heterozygous genotype was found to be associated with higher GS, as well as with the presence of distant metastases. The analysis of association between rs2910164 and the serum PSA level at diagnosis has shown statistically significant difference in genotype distribution among subgroups of patients with high (PSA>20 ng/ml) and low PSA (PSAGC = 2.22, 95% CI 1.24–3.97; ORCC = 0.47, 95% CI 0.13–1.68). When comparing genotype distributions among PCa and BPH patients, no statistically significant difference was found. Nevertheless, for log-additive model of inheritance, statistical
127
trend of significance (0.05