ABSTRACT: Molecular profiling of peripheral blood is associated with circulating tumor cells content and poor survival in metastatic castration-resistant prostate cancer
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:Peripheral blood from 62 men with castration resistant prostate cancer was collected between 8/2006 and 6/2008. A panel of 168 inflammation-related and prostate cancer related genes was assessed with quantitative PCR to assess biomarkers predictive of survival. qPCR profiling of whole blood from patients with castration-resistant prostate cancer.
Project description:Bulk RNA sequencing of peripheral blood neutrophils from prostate cancer at different stages of disease progression, including localized disease, hormone-sensitive- and castration-resistant metastatic prostate cancer
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.
Project description:Peripheral blood from 62 men with castration resistant prostate cancer was collected between 8/2006 and 6/2008. A panel of 168 inflammation-related and prostate cancer related genes was assessed with quantitative PCR to assess biomarkers predictive of survival.
Project description:New approaches that generate long-lasting therapeutic responses in therapy-resistant metastatic cancer patients are urgently needed. To address this challenge, we developed SpotNeoMet, a novel data-driven pipeline that systematically identifies recurrently presented neopeptides in treatment-resistant patients. We identified seven therapy resistance mutations predicted to produce neo-peptides presented by common HLAs. Using HLA-immunopeptidomics, we discovered three novel neopeptides derived from Androgen Receptor (AR) H875Y, a common metastatic castration-resistant prostate cancer (mCRPC) mutation. We validated these neoantigens as highly immunogenic and then isolated and characterized cognate T-cell receptors (TCRs) from healthy donor peripheral blood mononuclear cells. We demonstrated that AR H875Y specific TCRs are highly specific and kill prostate cancer cells presenting AR neo-peptides in vitro and in vivo. Our new pipeline identifies novel immunotherapy targets and potential treatment options for mCRPC patients. Moreover, SpotNeoMet offers a systematic route to identify 'HLA-peptide' pairs and their cognate TCRs across treatment-resistant cancers.
Project description:The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment. We performed a pilot study to evaluate the feasibility of isolation and genomic profiling of CTCs in castration-resistant prostate cancer. CTCs in 7.5 mLs of blood in 20 castration-resistant metastatic prostate cancer patients were enumerated using CellSearch. Additional 10-20 mLs of blood from 12 patients positive for CTCs were subjected to immunomagnetic enrichment and fluorescence activated cell sorting (IE/FACS) to isolate pools of ~20 CTCs. Genomic DNA of CTCs was subjected to whole genome amplification followed by gene copy number analysis via array comparative genomic hybridization (aCGH). Archival primary tumor biopsy samples available from 2 patients were also subjected to aCGH.
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:We analyzed the global gene expression pattern of Tregs between healthy donors and prostate cancer patients. We found that genes related to cell cycle, cellular proliferation, immune responses, hematological system development and function were differentially expressed in Tregs from prostate cancer patients. Total RNA samples of Tregs, isolated from peripheral blood, were obtained from three separate healthy donors and three metastatic castration-resistant prostate cancer patients. Global gene expression pattern was examined by performing GeneChip microarray hybridization. Genes differentially expressed between the two groups of donors were sorted and categorized based on their biological functions.
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.
