Project description:In order to develop novel biomarkers in prostate cancer, we applied a competing endogenous RNA (ceRNA) microarray to identify differentially expressed mRNAs, circRNAs and lncRNAs in PCa tissue.
Project description:The purpose of this study are: - To identify new biomarkers specific for prostate cancer (PCa) that can be used as diagnostic markers in the urine of individuals with high probability of PCa (abnormal PSA and/or digital rectal examination). - To validate the utility of these new biomarkers, as well as others already known such as PCA3, fusion gene TMPRSS2-ERG, GOLPH2 and SPINK1. - To establish a prediction model for the diagnosis of PCa based on the expression of these biomarkers. - To validate this model within the framework of an opportunist programme of early diagnosis. - Within the framework of this programme, to associate a series of social-demographic, antropometric, life-style and occupational variables for establishing a risk model predictor that could be associated with the model based on the biomarkers. Methodology: The study is divided in three phases based on three different cohorts of patients: -Phase 1. Identification of biomarkers. This phase includes 60 patients (10 normal prostates and 50 PCa). Form these tumors a screening of miRNAs will be performed. -Phase 2. Validation of the new biomarkers and others already known by means qRT-PCR on urine samples from 300 patients (200 with histological diagnosis of PCa and 100 with an histological negative result). -Phase 3. Prospective validation in a prospective cohort iof 1065 patients included in an opportunist programme of early detection of PCa.
Project description:The purpose of this study are: - To identify new biomarkers specific for prostate cancer (PCa) that can be used as diagnostic markers in the urine of individuals with high probability of PCa (abnormal PSA and/or digital rectal examination). - To validate the utility of these new biomarkers, as well as others already known such as PCA3, fusion gene TMPRSS2-ERG, GOLPH2 and SPINK1. - To establish a prediction model for the diagnosis of PCa based on the expression of these biomarkers. - To validate this model within the framework of an opportunist programme of early diagnosis. - Within the framework of this programme, to associate a series of social-demographic, antropometric, life-style and occupational variables for establishing a risk model predictor that could be associated with the model based on the biomarkers.
Project description:Prostate cancer (PCa) remains a prevalent and deadly disease. The histology-based Gleason score (GS) of PCa tissue biopsy is the most accurate predictor of disease aggressiveness and an important measure to guide decision-making with respect to treatment strategies and patient management. However, inherent variability associated with PCa tumour sampling and the subjective determination of the GS are still key challenges precluding accurate diagnostication and prognostication. Thus, novel molecular signatures are urgently needed to distinguish between indolent and aggressive forms of PCa for better patient management and outcomes. Herein, we have used label-free LC-MS/MS-based proteomics to profile the proteome of 50 PCa tissues spanning five GS-based PCa grades (n = 10 per group) relative to five tissues from individuals with benign prostatic hyperplasia (BPH). Over 2,000 proteins were consistently identified albeit at different levels between and within the patient groups, revealing biological processes associated with specific grades. Excitingly, a panel of 11 prostate-derived proteins including IGKV3D-20, RNASET2, TACC2, ANXA7, LMOD1, PRCP, GYG1, NDUFV1, H1FX, APOBEC3C, CTSZ displayed the potential to accurately stratify patients displaying low and high GS. This is the first study to characterise the prostate tissue proteome signatures of the five PCa grades relative to BPH. We report a panel of proteins that accurately can distinguish low and high GS PCa tissues. These promising proteins can be further explored as candidate biomarkers for PCa aggressiveness.
Project description:This study aimed to identify gene signatures induced by enzalutamide (ENZA) in hormone-sensitive (LNCaP) and hormone-resistant prostate cancer (PCa) cells. LNCaP and C4-2 cells were treated with ENZA alone or in combination with androgen deprivation therapy (ADT) and radiation (XRT). Through gene expression profiling, we identified that ENZA alone or in combination with ADT enhanced the effect the effect of XRT through immune-related pathways in LNCaP cells and metabolic pathways in C4-2 cells.Kaplan-Meier curve and Cox propotional hazard models showed that low expression of all the candidate genes except PTPRN2 were associated with tumor progression and recurrence in a PCa cohort.
Project description:Copy number variations (CNVs) in the human genome have been linked to various carcinomas including prostate cancer (PCa). This study was conducted to identify CNVs in high grade PCa. We performed a pilot genome-wide CNV analysis in 36 subjects (18 high grade PCa and 18 benign prostatic hyperplasia) using array comparative genomic hybridization (aCGH) technique. Array results were validated using PCR-based copy number counting method. A total of 339 CNV regions were found to be unique to PCa subjects in this cohort (P < 0.05). Data segregation and filtering revealed six putative CNV loci associated with susceptibility to PCa. Of these, four were rare (1q21.3, 15q15, 3q27.2 and 7p12.1) and one was a novel copy number gain (12q23.1), harbouring genes such as the ARNT, THBS1, SLC5A8 and DDC which are crucial in the p53 and cancer pathways. Another CNV was a loss at 8p11.21 which contains the SFRP1 gene from the Wnt signalling pathway, known for its interaction with androgen receptors as reported for urological malignancy. Cross comparison analysis with genes already known to be associated with PCa revealed significant CNVs involved in crucial biological processes that elicit cancer pathogenesis via cytokine production, disease progression through endothelial cell proliferation and xenobiotic metabolism. In conclusion, these findings suggest that the CNV regions identified could provide an insight into the development of high grade PCa.
Project description:Prostate cancer (PCa) is heterogeneous containing both phenotypically differentiated and undifferentiated tumor cells. An important unanswered question is whether these two populations of PCa cells are functionally different. Here we report the distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (i.e., PSA+) and low (PSA-/lo) levels of the differentiation marker PSA (prostatespecific antigen). PSA-/lo PCa cells are quiescent and resistant to multiple stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity in male mice. They preferentially express stem cell-associated genes and can undergo asymmetric cell division generating PSA+ cells. Importantly, PSA-/lo PCa cells can initiate robust tumor development in castrated hosts, survive androgen deprivation, and harbor highly tumorigenic castration-resistant PCa cells that can be further enriched using the ALDH+CD44+α2β1+ phenotype. In contrast, PSA+ PCa cells possess more limited tumor-propagating capacity, mainly undergo symmetric division, and are sensitive to castration. Together, our study suggests that PSA-/lo and PSA+ PCa cells are functionally distinct and PSA-/lo cells may represent one critical source of castration-resistant PCa cells. There are two sets of samples in this study corresponding to two different prostate cancer cell lines LNCaP and LAPC9. Both LNCaP and LAPC9 sets include 3 technical triplicates each that were performed onvdual color arrays and each individual array includes comparison between PSA- (Cy5) and PSA+ (Cy3) cells of the respective cell line.
Project description:MDA PCa 2b is an androgen-responsive, AR-positive prostate cancer cell line. Here, we report the generation of an Enzalutamide-resistant derivative, MDA PCa 2b-EnzaR. Gene expression of MDA PCa 2b-EnzaR compared to its parental counterpart were assessed by short-read RNA sequencing.