FP109PROSTATE CANCER IS CHARACTERIZED BY A DYSREGULATION OF THE IMMUNE RESPONSE

Abstract

Introduction and Aims: Prostate cancer (PCa) is the second‐leading cause of cancer‐associated mortality in the general population and in kidney transplant recipients. To date the role of immune system in the development and progression of this neoplasia is still unclear. The aim of our study was to investigate, using a transcriptomic approach, the eventual involvement of circulating immune cells dysregulation in PCa with deregulated pathways to allow the identification of potentially useful biomarkers. Methods: To this purpose, 34 patients diagnosed with Gleason 6° PCa undergoing prostate resection and 20 patients with benign prostatic hyperplasia (BPH) were enrolled. In addition, 33 healthy volunteers, matched to the study groups for the main demographic features, were chosen as controls. Peripheral blood mononuclear cells were harvested at the time of diagnosis. Transcriptomic analysis was performed by T T Agilent echnologies on 8 randomly selected patients/group. he results were analyzed statistically by GeneSpringGX 12.5 software applying a fold change (FC)>2.5 and a false discovery rate<5% and analyzed functionally by Ingenuity Pathway Analysis software (IPA). The microarray data were validated by qPCR and confocal microscopy in an independent set of patients and controls. Results: We identified 407 genes differentially expressed between subjects with and without PCa. The analysis identified the main biological functions significantly associated with PCa: organismal injury and abnormalities (p range=1.99E‐02‐4.93E‐06, 289 genes), immunological disease (p range=1.82E‐02‐1.98E‐05,45 genes) andinflamma‐tory disease (p range=1.93E‐02‐1.98E‐05,40 genes) featuring the immunological profile of PCa patients. Interestingly, among the early up‐regulated genes in PCa patients appeared different proteins involved in the control of cell proliferation, including the cell differentiation inhibitor 1 (ID1,FC=+17.1) and the differentiation inhibitor 3, (ID3, FC=+3.27). qRT‐PCR was conducted to examine the gene expression levels in an independent cohort of subjects and confirmed the increased gene expression of ID1 and ID3 in total lymphomonocytes (p=0.04) and especially in CD3+ lymphocytes (p=0.025) of PCa patients versus controls. To assess the correlation between the circulating ID1 and ID3 expression and their protein expression in prostate biopsy, we performed an indirect immunofluorescence in PCa and BPH. In PCa ID1 and ID3 expression was significantly upregulated (ID1:1500 6221 vs 603 634 %pixels/area, ID3:1000 6221 vs 303 622 %pixels/area, p<0.04) and were confined to the infiltrating lymphocytes. Conclusions: Our data suggest that patients with PCa present an alteration of the immune response, characterized by an increased expression of ID1 and ID3. The evaluation of immunosuppressive therapy effect on these two potential biomarkers in a large population of kidney transplant recipients is warranted.