Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA156569 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE32967: Modeling lethal prostate cancer variant with small cell carcinoma features [expression profile] GSE33053: Modeling lethal prostate cancer variant with small cell carcinoma features [genomic profile] Refer to individual Series
2012-01-01 | E-GEOD-33054 | biostudies-arrayexpress
Project description:Modeling lethal prostate cancer variant with small cell carcinoma features [expression profile]
| PRJNA155517 | ENA
Project description:Small cell carcinoma, often found with neuroendocrine features, is a lethal cancer variant, as seen for small cell lung cancer and treatment-resistant late-stage small cell neuroendocrine prostate cancer (SCPC). A genome-wide CRISPR dependency screen using SCPC models generated through human prostate cell transformation identifies a requirement for the transcription factor E2F3 in this cancer subtype. E2F3 dependency is linked to RB inactivation, an event that occurs nearly universally across small cell cancers. The requirement for E2F3 is shared by RB-deficient cells originating from the prostate, lung and adnexa (ovary and fallopian tube). In RB-deficient cancer cells, E2F3 inhibition restrains cell cycle progression, proliferation, and tumor growth in vivo. Inhibition of de novo pyrimidine synthesis limits E2F3 expression and suppresses small cell cancer proliferation in culture. Directly or indirectly targeting E2F3 to leverage a pan-cancer synthetic lethality resulting from RB inactivation represents a potential treatment strategy.
2026-03-04 | GSE318281 | GEO
Project description:Prostate cancer is the Prostate cancer is the most prevalent cancer in men. However, the majority of prostate cancers diagnosed today are indolent with 14% of patients diagnosed with lethal prostate cancer. It is of great importance to determine the molecular features that are involved in the aggressiveness of prostate cancers. To this end, we found that through SWATH-MS proteomics analyses of 108 well-preserved frozen prostate tissues of various disease states, tmost prevalent cancer in men. However, the majority of prostate cancers diagnosed today are indolent with 14% of patients diagnosed with lethal prostate cancer. It is of great importance to determine the molecular features that are involved in the aggressiveness of prostate cancers. To this end, we deployed SWATH-MS proteomics analyses of 108 well-preserved frozen prostate tissues of various disease states.
2022-02-28 | PXD002306 | Pride
Project description:MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC including the small cell prostate carcinoma (SCPC) variant with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can both arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. Expression profiling by high throughput sequencing of experimentally generated human tumors with mixed NEPC and prostate adenocarcinoma. Gene expression analysis of laser capture microdissected NEPC and adenocarcinoma from three independent engineered human tumors of mixed NEPC and prostate adenocarcinoma phenotype.
2016-02-06 | E-GEOD-77624 | biostudies-arrayexpress
Project description:Aggressive variant prostate cancer is characterized by poor clinical outcomes and profound molecular heterogeneity. In this study, we performed integrative genomic analyses of AVPC to identify potential drug sensitivities and molecular features associated with platinum response.
2026-01-31 | GSE309839 | GEO
Project description:Purpose: Clinicopathologic features and biochemical recurrence are sensitive, but not specific, predictors of metastatic disease and lethal prostate cancer. We hypothesize that a genomic expression signature detected in the primary tumor represents true biological potential of aggressive disease and provides improved prediction of early prostate cancer metastasis. Methods: A nested case-control design was used to select 639 patients from the Mayo Clinic tumor registry that underwent radical prostatectomy between 1987 and 2001. A genomic classifier (GC) was developed by modeling differential RNA expression using 1.4 million feature high-density expression arrays of men enriched for rising PSA after prostatectomy, including 213 that experienced early clinical metastasis after biochemical recurrence. A training set was used to develop a random forest classifier of 22 markers to predict for cases - men with early clinical metastasis after rising PSA. Performance of GC was compared to prognostic factors such as Gleason score and previous gene expression signatures in a withheld validation set. Results: Expression profiles were generated from 545 unique patient samples, with median follow-up of 16.9 years. GC achieved an area under the receiver operating characteristic curve of 0.75 (0.67 - 0.83) in validation, outperforming clinical variables and gene signatures. GC was the only significant prognostic factor in multivariable analyses. Within Gleason score groups, cases with high GC scores experienced earlier death from prostate cancer and reduced overall survival. The markers in the classifier were found to be associated with a number of key biological processes in prostate cancer metastatic disease progression. Conclusion: A genomic classifier was developed and validated in a large patient cohort enriched with prostate cancer metastasis patients and a rising PSA that went on to experience metastatic disease. This early metastasis prediction model based on genomic expression in the primary tumor may be useful for identification of aggressive prostate cancer. 545 formalin-fixed paraffin-embedded (FFPE) tissue samples from primary prostate cancer obtained from Radical Prostatectomy.
2013-07-01 | E-GEOD-46691 | biostudies-arrayexpress
Project description:MYCN amplification and overexpression are common in neuroendocrine prostate cancer (NEPC). However, the impact of aberrant N-Myc expression in prostate tumorigenesis and the cellular origin of NEPC have not been established. We define N-Myc and activated AKT1 as oncogenic components sufficient to transform human prostate epithelial cells to prostate adenocarcinoma and NEPC including the small cell prostate carcinoma (SCPC) variant with phenotypic and molecular features of aggressive, late-stage human disease. We directly show that prostate adenocarcinoma and NEPC can both arise from a common epithelial clone. Further, N-Myc is required for tumor maintenance and destabilization of N-Myc through Aurora A kinase inhibition reduces tumor burden. Our findings establish N-Myc as a driver of NEPC and a target for therapeutic intervention. Expression profiling by high throughput sequencing of experimentally generated human tumors with mixed NEPC and prostate adenocarcinoma.
2016-02-06 | GSE77624 | GEO
Project description:Prostate cancers with clinical features of small cell prostate carcinomas (SCPC) but diverse morphologies share chemotherapy responsiveness with SCPC. We prospectively collected tumor tissues from clinically defined, morphologically diverse, aggressive variant prostate cancers (AVPCa) to determine if they also share molecular features with SCPC
2015-10-10 | GSE73902 | GEO