Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional PanCancer pathways of localized early prostate cancer

ABSTRACT: The management of intermediate-risk early prostate cancer (PCa) is challenging due to the difficulty in distinguishing indolent from aggressive tumors. This study explores the impact of genomic alterations on the tumor and its microenvironment (TME). We performed multi-omic profiling in a cohort of 53 localized PCa using targeted sequencing, transcriptional and proteomic spatial profiling. Somatic mutations and copy number alterations in RB1 (21%), PTEN (18%), and TP53 (9%) were identified. Kaplan-Meier analysis revealed that alterations in the RB and Cell Cycle pathways, particularly aberrations in PTEN, TP53, or RB1, were associated with shorter biochemical recurrence-free survival (p < 0.001). Spatial proteomic analysis demonstrated a complex immune landscape in patients with mutations. The tumor compartment demonstrated higher expression of immune checkpoint markers, T-cell activation proteins, and proliferation markers; and a TME that is enriched with CD8+ T cells and antigen-presenting cells, but also with immunosuppressive M2 macrophages, suggesting adaptive immune resistance. Our analysis demonstrates that genomic alterations in PTEN, TP53, or RB1 are not only prognostic for poor outcomes but also actively shape a unique, immunologically active yet suppressed TME.

ORGANISM(S): Homo sapiens

PROVIDER: GSE317424 | GEO | 2026/01/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptional Cancer Immune pathways of localized early prostate cancer

Project description:The management of intermediate-risk early prostate cancer (PCa) is challenging due to the difficulty in distinguishing indolent from aggressive tumors. This study explores the impact of genomic alterations on the tumor and its microenvironment (TME). We performed multi-omic profiling in a cohort of 53 localized PCa using targeted sequencing, transcriptional and proteomic spatial profiling. Somatic mutations and copy number alterations in RB1 (21%), PTEN (18%), and TP53 (9%) were identified. Kaplan-Meier analysis revealed that alterations in the RB and Cell Cycle pathways, particularly aberrations in PTEN, TP53, or RB1, were associated with shorter biochemical recurrence-free survival (p < 0.001). Spatial proteomic analysis demonstrated a complex immune landscape in patients with mutations. The tumor compartment demonstrated higher expression of immune checkpoint markers, T-cell activation proteins, and proliferation markers; and a TME that is enriched with CD8+ T cells and antigen-presenting cells, but also with immunosuppressive M2 macrophages, suggesting adaptive immune resistance. Our analysis demonstrates that genomic alterations in PTEN, TP53, or RB1 are not only prognostic for poor outcomes but also actively shape a unique, immunologically active yet suppressed TME.

2026-01-31 | GSE317416 | GEO

Bulk RNA-seq of castration-resistant tumors from Ptenpc-/- mice reconstituted with either F10fl/fl or F10fl/fl; LysM-Cre+ mice

Project description:PTEN is one of the most altered tumor suppressor genes in human prostate cancer (PCa). Prostate specific-Pten-deficient mouse models develop prostate cancer eventually progressing to castration-resistant prostate cancer (CRPC), also due to alterations of the tumor immune infiltrate. By using single-cell RNA-seq, we report the identification of a subset of CD84+; CD11b+; Ly6G+; Ly6Clow immunosuppressive neutrophils that secreted the coagulation factor X (FX) into the prostate TME to directly promote PCa growth.

2024-08-21 | GSE272967 | GEO

Multiple chromoanasynthesis in a rare case of sporadic renal leiomyosarcoma: case report

Project description:Renal leiomyosarcomas (LMS) are extremely rare neoplasms with aggressive behaviour and poor survival prognosis. The most frequent somatic events in leiomyosarcomas are mutations in TP53, RB1, ATRX and PTEN genes, chromosomal instability and chromoanagenesis. By using chromosomal microarray analysis we identified monosomy of chromosomes 3 and 11, gain of Xp (ATRX) arm and three chromoanasynthesis regions (6q21-q27, 7p22.3-p12.1 and 12q13.11-q21.2), with MDM2 and CDK4 oncogenes copy number gains, whereas no CNVs or tumor specific SNVs in TP53, RB1 and PTEN genes were observed.

2020-06-04 | GSE151766 | GEO

Comparision of PBMC from PTEN loss and WT glioblastoma patients

Project description:Glioblastoma (GBM) is a lethal type of brain tumor that is resistant to immunotherapy. Genetic profiling studies have indicated that the tumorigenesis of GBM is linked to somatic genomic alterations in key driver genes, such as TP53, PTEN, CDKN2A, RB1, EGFR, and NF1. These genes regulate critical pathways related to cell growth and resistance to immunotherapy, including the use of immune checkpoint inhibitors (ICIs). One reason for resistance to ICI therapy may be the presence of immunosuppressive myeloid cells, including macrophages and myeloid-derived suppressor cells (MDSCs). We conducted an unbiased analysis to identify specific genetic alterations in GBM cells that may influence MDSC biology and contribute to resistance against immunotherapy.

2026-01-01 | GSE286354 | GEO

Mechanisms of Resistance to Prostate-Specific Membrane Antigen-Targeted Radioligand Therapy in a Mouse Model of Prostate Cancer

Project description:Purpose: Prostate-specific membrane antigen-targeted radioligand therapy (PSMA-RLT) is effective against prostate cancer (PCa), but all patients relapse eventually. Poor understanding of the underlying resistance mechanisms represents a key barrier to development of more effective RLT. We investigate the proteome and phosphoproteome in a mouse model of PCa to identify signaling adaptations triggered by PSMA-RLT. Experimental Design: Therapeutic efficacy of PSMA-RLT was assessed by tumor volume measurements, time to progression, and survival in C4-2 or C4-2 TP53-knockout tumor-bearing Nod scid gamma mice. Two days post-RLT, the (phospho)proteome was analyzed by mass spectrometry. Results: PSMA-RLT significantly improved disease control in a dose-dependent manner. (Phospho)proteomic datasets revealed activation of genotoxic stress response pathways, including deregulation of DNA damage/replication stress response, TP53, androgen receptor, PI3K/AKT, and MYC signaling. C4-2 TP53-knockout tumors were less sensitive to PSMA-RLT than parental counterparts, supporting a role for TP53 in mediating RLT responsiveness. Conclusions: We identified signaling alterations that may mediate resistance to PSMA-RLT in a PCa mouse model. Our data enable the development of rational synergistic RLT-combination therapies to improve outcomes for PCa patients.

2020-11-04 | MSV000086408 | MassIVE

Hierarchical synergy of Pten, p53 and Rb pathways in high-grade astrocytoma induced in adult brain

Project description:Mutations in the PTEN, TP53 and RB1 pathways are obligate events in the pathogenesis of human glioblastomas, the highest grade of astrocytoma. To investigate synergy between these tumor suppressors in mice, we induced various combinations of compound deletions conditionally in astrocytes and neural precursors in the mature brain. The resulting highly penetrant astrocytomas showed a spectrum of histopathological variation reminiscent of human tumors, and ranged from grade III to grade IV (glioblastoma). Secondary somatic mutations varied depending on the combination of initiating deletions and were relevant to human disease. Receptor tyrosine kinase amplifications were frequent in tumors initiated by combined conditional deletion of Pten and Tp53, but not when Rb, Pten and Tp53 were simultaneously deleted. Multiple mutations within PI3K and Rb pathways were acquired, however, Mapk activation was not consistently detected in astrocytomas. Gene expression profiling revealed striking similarities to previously described human astrocytoma subclasses. A subset of astrocytomas initiated outside of proliferative niches in the adult brain. Gene expression of 8 human brain samples including 2 normal brainstem and 6 brainstem low-grade gliomas were profiled using HG-U133 plus 2 arrays. Gene expression of 38 mouse tumor samples, including 24 Pten;p53 double knockout and 14 Pten;p53;Rb1 triple knockout, were profiled using Affymetrix Mouse Genome 430 v2 arrays. Copy number changes of 51 double knockout tumor samples were analysed using Roswell Park Cancer Institute 6.5k BAC arrays. Copy number changes of 21 triple knockout tumor samples were analysed using Agilent mouse genome CGH mocirarray 244A.

2011-03-23 | E-GEOD-22927 | biostudies-arrayexpress

RB1 loss promotes a noncanonical activator function of LSD1 and sensitizes castration-resistant prostate cancer to LSD1 inhibition [RNA-seq]

Project description:Genomic loss of RB1 is a common alteration in castration-resistant prostate cancer (CRPC) and is associated with poor patient outcomes. RB1-loss is also a driver event that promotes the neuroendocrine transdifferentiation of prostate cancer (PCa). The loss of Rb protein disrupts the Rb-E2F repressor complex and thus hyperactivates E2F transcription activators. While the impact of RB1-loss on PCa progression and linage plasticity has been previously studied, the underline mechanisms remain unclear. Using an integrated cistromic and transcriptomic analysis, we have characterized Rb activities in multiple CRPC models by identifying Rb directly regulated genes and revealed that Rb has distinct binding sites and targets in TP53-mutated CRPC. Significantly, we show that RB1-loss promotes the noncanonical activator function of LSD1/KDM1A, which stabilizes chromatin binding of E2F1, and hence sensitizes CRPC tumor to the LSD1 inhibitor treatment. These results provide new molecular insights of Rb activity in PCa progression and suggest LSD1 as a potential therapeutic target in CRPC with RB1-loss.

2022-01-14 | GSE176403 | GEO

RB1 loss promotes a noncanonical activator function of LSD1 and sensitizes castration-resistant prostate cancer to LSD1 inhibition [ChIP-seq]

2022-01-14 | GSE176402 | GEO

Defining the immunophenotype within the clear cell renal cell carcinoma tumour microenvironment to guide immune checkpoint blockade

Project description:We performed spatial transcriptome profiling (ST-seq) on nine fresh frozen tissue sections to understand the immunophenotypes; immune cell types, states and their spatial location within the clear cell renal cell carcinoma (ccRCC) tumour microenvironment (TME).

2023-08-16 | E-MTAB-12767 | biostudies-arrayexpress

PanCancer Immune panel on treated tumors

Project description:Our data showed that ENT broadly impacted multiple populations of immune cells within the TME. Thus, we performed general immune transcriptome profiling on whole tumors isolated from the neu-N model using a PanCancer immune-profiling gene panel for the NanoString platform.

2018-10-10 | GSE121031 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data