Project description:Prostate cancer (PCa) is a common cancer and remains the second leading cause of cancer-associated mortality in men. To investigate the involvement of differentially expressing genes in PCa with deregulated pathways to allow earlier diagnosis of the disease, transcriptomic analyses of differential expression genes in Fine-Needle Aspiration (FNA) biopsies were for discrimination of PCa from benign prostatic hyperplasia (BPH). The RNA samples were extracted from four PCa biopsy samples and four BPH biopsy controls for microarray profiling and performed in Affymetrix Human U133 Plus 2 arrays for gene expression profiling analysis. Microarray data were analyzed using GeneSpring GX 10 (Agilent).On average, we detected expression of 47,000 transcripts.Under the criteria fold change > 2 or < 0.5, we obtained 1819 differential expressed genes(DEGs).Hierarchy cluster analysis also indicated that the 8 samples were distributed into two clusters, 4 PCa samples in one cluster and 4 BPH samples in another cluster.Then,qRT-PCR validation of the DEGs in PCa tissue and prostate cancer cells.The results revealed that grouping was reasonable and the data can be directly applied to further analysis.
Project description:GENPROS aims to analyse the outcomes of patients with rare gene mutations in the cancer predisposition genes, BRCA1, BRCA2, HOXB13, and Lynch Syndrome, after a diagnosis of and treatment for prostate cancer (PCa). The study includes a cohort of gene mutation carriers with PCa matched with a control group of men with PCa who are known not to carry a mutation in the same gene. Clinical data regarding treatment and patient outcome will be collected retrospectively and prospectively. Archived tumour samples will also be collected for tumour profiling. A blood or saliva sample will be taken, if the participant consents to this part of the study, for genetic profiling to investigate any association of other inherited factors with PCa outcomes. Information obtained from this study will be of critical importance to support clinical trials investigating the most appropriate management of PCa in this group of patients at increased risk of prostate cancer.
Project description:To identify prostate cancer-specific gene expression, we have employed whole cDNA microarray expression profiling between benign prostate hypertrophy and prostate cancer. We performed needle biopsy of patients with prostatic hyperplasia who were suspected as prostate cancer for minor high level (4.0-10 ng/ml). As a result of needle biopsy, we used the tissue of patients with prostatic hyperplasia that prostate cancer was denied for cDNA microarry analysis. Furthermore, we also performed needle biopsy of patients that prostate cancer should have been strongly suspected because of high PSA. Needle biopsies were performed after we obtained informed consent from patients with the document approved from the Graduate School of Medical Science, Kanazawa University. Gene expression profile was determied in each of normal prostate samples and prostate cancer samples. Then the profiles were compared between normal prostate samples and prostate cancer samples.
Project description:Introduction: Androgen deprivation therapy (ADT) remains the primary treatment for advanced prostate cancer (PCa). The efficacy of ADT has not been rigorously evaluated by demonstrating suppression of prostatic androgen activity at the target tissue and molecular level. We determined the efficacy and consistency of medical castration in suppressing prostatic androgen levels and androgen-regulated gene-expression. Design: Androgen levels and androgen-regulated gene-expression (by microarray-profiling, qRT-PCR and immunohistochemistry) were measured in prostate samples from a clinical trial of short-term castration (1 month) using the GnRH-antagonist, Acyline, vs. placebo in healthy men. To assess the effects of long-term ADT, gene-expression measurements were evaluated at baseline and after 3, 6 and 9 months of neoadjuvant ADT in prostatectomy samples from men with localized PCa. Results: Medical castration reduced tissue androgens by 75% and reduced the expression of several androgen-regulated genes (NDRG1, FKBP5, TMPRSS2). However, many androgen-responsive genes, including the androgen receptor (AR) and PSA, were not suppressed after short-term castration, nor after 9 months of neoadjuvant ADT. Significant heterogeneity in PSA and AR protein expression was observed in PCa samples at each time-point of ADT. Conclusions: Medical castration based on serum testosterone levels cannot be equated with androgen ablation in the prostate microenvironment. Standard androgen deprivation does not consistently suppress androgen-dependent gene-expression. Suboptimal suppression of tumoral androgen activity may lead to adaptive cellular changes allowing PCa cell survival in a low androgen environment. Optimal clinical efficacy will require testing of novel approaches targeting complete suppression of systemic and intracrine contributions to the prostatic androgen microenvironment. Keywords: prostate, androgen, Acyline, microarray, immunohistochemistry
Project description:DNA methylation of prostatic normal cells (PrEC), normal mammary epithelial cells (HMEC), prostate cancer cell line (MDA-PCa-2b), and breast cancer cell lines (BT474 and MDA-MB-231) was analyzed by MeDIP-on-chip analysis. DNA obtained from each cells was immunoprecipitated by anti 5-methylcytidine antibody. IP DNA and input DNA were labeled with Cy5 and Cy3, respectively, and then analyzed by using human CpG island microarray provided by Agilent Technologies.
Project description:Prostate cancer (PCa) is one of the most prevalent cancer types in men worldwide. However, the main diagnostic tests available for PCa have limitations and need biopsy for histopathological confirmation of the disease. The prostate-specific antigen (PSA) is the main biomarker used for PCa early detection, but an elevated serum concentration is not cancer-specific. Therefore, there is a need for discovery of new non-invasive biomarkers that can accurately diagnose PCa. Here, we used trichloroacetic acid-induced protein precipitation and liquid chromatography-mass spectrometry to profile endogenous peptides in urine samples from patients with PCa (n = 33), benign prostatic hyperplasia (n = 25), and healthy individuals (n = 28). Receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic performance of urinary peptides. In addition, proteasix tool was used for in silico prediction of protease cleavage sites. We found five urinary peptides derived from uromodulin significantly altered between the study groups, all of which were less abundant in the PCa group. In addition, urinary peptides outperformed PSA in discriminating between malignant and benign prostate conditions (AUC = 0.847), showing high sensitivity (81.82%) and specificity (88%). Overall, our study allowed the identification of urinary peptides with potential for use as non-invasive biomarkers in PCa diagnosis.
Project description:Gene expression profiling of the prostate biopsy samples (cancer and adjacent normal tissues) from African American prostate cancer patients