ABSTRACT: Integrative Clinical Sequencing Analysis of Metastatic Castration Resistant Prostate Cancer Reveals a High Frequency of Clinical Actionability
Project description:Integrative Clinical Sequencing Analysis of Metastatic Castration Resistant Prostate Cancer Reveals a High Frequency of Clinical Actionability
Project description:Supporting ChIP-Seq data for the article "The genomic landscape of metastatic castration-resistant prostate cancers" by Dessel et al. (Nat. Comm. 2019) reveals multiple distinct genotypes with potential clinical impact
Project description:To elucidate the regulation of NSD2 in metastatic castration-resistant prostate cancer(CRPC), we performed Hi-C against castration-sensitive prostate cancer cell line LNCaP and metastatic castration-resistant prostate cancer cell lines, PC3 respectively. In metastatic CRPC, we found specific regions of activation with epigenetic changes.
Project description:Prostate cancer is one of the major cancers that seriously affect men's health. It has high morbidity and high mortality, but there is still no ideal molecular markers for the diagnosis and prognosis of prostate cancer. Castration-resistant prostate cancer is associated with wide variations in survival. To determine whether differentially expressed circRNAs in plasma exosomes can be used as a novel biomarker for castration-resistant prostate cancer prognosis, we performed high-throughput circRNA sequencing on 15 pairs of plasma exosomes from 30 metastatic castration-resistant prostate cancer patients, with or without early progression, to screen differentially expressed circRNAs.
Project description:To elucidate the regulation of NSD2 in metastatic castration-resistant prostate cancer(CRPC), we performed ChIP-seq of H3K36me2, H3K27me3, H3K4me1, H3K4me3,H3K27ac and NSD2 against castration-sensitive prostate cancer cell line LNCaP and metastatic castration-resistant prostate cancer cell lines, PC3 and DU145, respectively. In metastatic CRPC, we found specific regions of activation with epigenetic changes.
Project description:To elucidate the regulation of NSD2 in metastatic castration-resistant prostate cancer(CRPC), we performed ChIP-seq of H3K36me2, H3K27me3, H3K4me1, H3K4me3,H3K27ac and NSD2 against castration-sensitive prostate cancer cell line LNCaP and metastatic castration-resistant prostate cancer cell lines, PC3 and DU145, respectively. In metastatic CRPC, we found specific regions of activation with epigenetic changes.
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. Androgen-deprivation therapy is the first-line treatment strategy for advanced prostate cancer. However, many tumors develop to castration-resistant prostate cancer (CRPC) and relapse. Thus, analyzing key factors for development of CRPC is important. We found PSF functions as RNA binding protein and transcription factor to promote castration-resistant tumor growth. High expression of PSF in metastatic prostate cancer tissue indicates the clinical relevance. In order to investigate the PSF function in CRPC cells, we performed gene expression in CRPC model cells derived from AR-positive prostate cancer cell lines after siPSF treatment.
Project description:EZH2 is frequently over-expressed in aggressive and metastatic solid tumors, including castration resistant prostate cancer (CRPC). We sought to determine EZH2-dependent gene expression programmes in prostate cancer progression, and found an intriguing functional switch of EZH2 from a repressor to an activator during CRPC development. We used microarrays to detail the global profiling of gene expression that are differentially regulated upon EZH2 depletion in two different prostate cancer cell lines. The androgen-dependent prostate cancer cell line LNCaP and the LNCaP-derived androgen-independent cell line LNCaP-abl (abl) were used for this study, as their transcription profiles strongly resemble that of clinical androgen-dependent and castration resistant prostate tumors, respectively. EZH2 was silenced by specific siRNAs in both cell lines, and total RNA was extracted and hybridized on Affymetrix microarrays.
Project description:The enumeration of circulating tumor cells (CTCs) in peripheral blood correlates with clinical outcome in castration-resistant prostate cancer (CRPC). We analyzed the molecular profiling of peripheral blood from 43 metastatic CRPC patients with known CTC content in order to identify genes that may be related to prostate cancer progression. Global gene expression analysis identified the differential expression of 282 genes between samples with ?5 CTCs vs <5 CTCs, 58.6% of which were previously described as over-expressed in prostate cancer (18.9% in primary tumors and 56.1% in metastasis). Those genes were involved in survival functions such as metabolism, signal transduction, gene expression, and cell growth, death, and movement. The expression of selected genes was evaluated by quantitative RT-PCR. This analysis revealed a two-gene model (SELENBP1 and MMP9) with a high significant prognostic ability (HR 6; 95% CI 2.61 - 13.79; P<0.0001). The combination of the two-gene signature plus the CTCs count showed a higher prognostic ability than neither CTCs enumeration nor gene expression alone (P<0.05). This study shows a gene expression profile in PBMNC is associated with CTCs count and clinical outcome in metastatic CRPC, describing genes and pathways potentially associated with CRPC progression. The complete database comprised the expression measurements of 43 metastatic castration-resistant prostate cancer (CRPC) samples and their asociation with the number of circulating tumor cells (CTCs). Twenty of them have a number circulating tumor cells (CTCs) greater than 5.
Project description:Background Metastatic hormone-naïve prostate cancer (mHNPC) is an infrequent form of this tumour type that is characterized by metastasis at the time of diagnosis and accounts for 50% of prostate cancer-related deaths. Despite the extensive characterization of localized and metastatic castration resistant prostate cancer (mCRPC), the molecular characteristics of mHNPC remain largely unexplored. Results Here we provide the first extensive transcriptomics characterization of mHNPC. We generated discovery and validation bulk and single-cell RNA-Seq datasets and performed integrative computational analysis in combination with experimental studies. Our results provide unprecedented evidence of the distinctive transcriptional profile of mHNPC and identify stroma remodelling as a predominant feature of these tumours. Importantly, we discover a central role for the transcription factor SOX11 in triggering a heterotypic communication that is associated to the acquisition of metastatic properties. Conclusions Our study will constitute an invaluable resource for a profound understanding of mHNPC that can influence patient management.
