Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Spatial Transcriptomics on prostate cancer heterogeneity

ABSTRACT: Intratumor heterogeneity is one of the biggest challenges in cancer treatment today. Here we investigate tissue-wide gene expression heterogeneity throughout a multifocal prostate cancer using the spatial transcriptomics (ST) technology. Utilizing a novel approach for deconvolution, we analyze the transcriptomes of nearly 6750 tissue regions and extract distinct expression profiles for the different tissue components, such as stroma, normal and PIN glands, immune cells and cancer. We distinguish healthy and diseased areas and thereby provide insight into gene expression changes during the progression of prostate cancer. Compared to pathologist annotations, we delineate the extent of cancer foci more accurately, interestingly without link to histological changes. We identify gene expression gradients in stroma adjacent to tumor regions that allow for re-stratification of the tumor microenvironment. The establishment of these profiles is the first step towards an unbiased view of prostate cancer and can serve as a dictionary for future studies.

PROVIDER: EGAS00001003001 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Similar Datasets

Homo sapiens

Project description:Gene expression profiles of reactive stroma in prostate cancer

| PRJNA106087 | ENA

Primary prostate organoid transcriptomic profile in co-culture with primary prostate stroma

Project description:Organotypic in vitro culture is useful to model mammalian disease in numerous tissues. Normal epithelial differentiation and carcinogenesis both undergo in vivo regulation by stroma, but current culture methods exclude stroma. To mimic this in vivo environment, we developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells supported increased organoid formation and expressed growth factors and WNT-related genes involved in epithelial differentiation. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Tumoroids derived from primary prostate cancer maintained differential expression of the prostate cancer marker AMACR only in the presence of stroma. Stroma-induced phenotypes were similar in all patients examined, yet maintained inter-patient heterogeneity in the degree of response. Addition of stroma to in vitro organoid culture recapitulated the in vivo microenvironment by inducing organization of benign organoids into branching structures and preserving prostate cancer phenotypes.

2018-05-30 | GSE115052 | GEO

Transcription profiling of prostate cancer samples using Affymetrix U133Plus2 array

Project description:Over one million prostate biopsies are performed in the U.S. every year. However, pathology examination is not definitive in a significant percentage of cases due limited diagnostic tumor. We have observed that the microenvironment of prostate tumor cells exhibits numerous differential gene expression changes and have asked whether such information can be used to distinguish “tumor” from “nontumor”. We initially compared expression analysis data (Affymetrix U133plus2) from 18 volunteer biopsy specimens to 17 specimens containing largely tumor-adjacent stroma and identified 964 significant (p_adj < 0.01 and B > 0) expression changes. These genes were filtered to eliminate possible aging-related genes and genes expressed in tumor cells > 10% of the stroma cell expression level leading to 23 candidate genes (28 Affymetrix probe sets). A classifier based on the 28 probe sets was tested on 289 independent cases, including 195 tumor-bearing cases, 99 nontumor cases (normal biopsies, normal autopsies, remote stroma as well as pure tumor adjacent stroma) all with accuracies >85%, sensitivities >90% and specificities >85%. These results indicate that the prostate cancer microenvironment exhibits reproducible changes useful for categorization as “tumor” and “nontumor”. For inquires please contact dmercola@uci.edu. Experiment Overall Design: Prostate cancer gene expression profiles were studied in this project. Total RNA from 154 prostate sample with various amount of different cell types were hybridized to Affymetrix U133Plus2 array. The percentage of different cell types were determined by a pathologist.

2009-09-11 | E-GEOD-17951 | biostudies-arrayexpress

Stromal molecular signatures of breast and prostate cancer

Project description:Primary tumor growth induces host tissue responses that are believed to support and promote tumor progression. Identification of the molecular characteristics of the tumor microenvironment and elucidation of its crosstalk with tumor cells may therefore be crucial for improving our understanding of the processes implicated in cancer progression, identifying potential therapeutic targets, and uncovering stromal gene expression signatures that may predict clinical outcome. A key issue to resolve, therefore, is whether the stromal response to tumor growth is largely a generic phenomenon, irrespective of the tumor type, or whether the response reflects tumor-specific properties. To address similarity or distinction of stromal gene expression changes during cancer progression, oligonucleotide-based Affymetrix microarray technology was used to compare the transcriptomes of laser-microdissected stromal cells derived from invasive human breast and prostate carcinoma. Invasive breast and prostate cancer-associated stroma was observed to display distinct transcriptomes, with a limited number of shared genes. Interestingly, both breast and prostate tumor-specific dysregulated stromal genes were observed to cluster breast and prostate cancer patients, respectively, into two distinct groups with statistically different clinical outcomes. By contrast, a gene signature that was common to the reactive stroma of both tumor types did not have survival predictive value. Univariate Cox analysis identified genes whose expression level was most strongly associated with patient survival. Taken together, these observations suggest that the tumor microenvironment displays distinct features according to the tumor type that provides survival-predictive value. 6 samples of stroma surrounding invasive breast primary tumors; 6 matched samples of normal stroma. 6 samples of stroma surrounding invasive prostate primary tumors; 6 matched samples of normal stroma.

2011-03-31 | E-GEOD-26910 | biostudies-arrayexpress

Mast cell-derived SAMD14 is a novel regulator of the human prostate tumor microenvironment

Project description:Mast cells (MCs) are important cellular components of the tumor microenvironment and are significantly associated with poor patient outcomes in prostate cancer and other solid cancers. The promotion of tumor progression partly involves heterotypic interactions between MCs and cancer-associated fibroblasts (CAFs) which combine to potentiate a pro-tumor extracellular matrix and promote epithelial cell invasion and migration. Thus far, the interactions between MCs and CAFs remains poorly understood. To identify molecular changes that may alter resident MC function in the prostate tumor microenvironment, we profiled the transcriptome of human prostate MCs, isolated from patient-matched non-tumor and tumor-associated regions of fresh radical prostatectomy tissue. Transcriptomic profiling revealed a distinct gene expression profile of MCs isolated from prostate tumor regions, including the downregulation of SAMD14, a putative tumor suppressor gene. Proteomic profiling revealed overexpression of SAMD14 in HMC-1 MCs altered the secretion of proteins associated with immune regulation and extracellular matrix processes. To assess MC biological function within a model of the prostate tumor microenvironment, HMC-1-SAMD14+ conditioned media was added to co-cultures of primary prostatic CAFs and prostate epithelium. HMC-1-SAMD14+ secretions were shown to reduce the deposition and alignment of matrix produced by CAFs and suppress pro-tumorigenic prostate epithelial morphology. Overall, our data presents the first profile of human MCs derived from patient prostate cancer specimens and identifies MC-derived SAMD14 as an important mediator of MC phenotype and function within the prostate tumor microenvironment.

2021-03-12 | PXD022782 | Pride

High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development (aCGH)

Project description:Prostate cancer discovery and translational research are hampered by a lack of preclinical models which accurately reproduce the biological heterogeneity observed in patients. Accordingly, we have established a bank of transplantable patient-derived prostate tumor xenograft lines, using subrenal capsule grafting of human tumor tissue into immuno-deficient mice. This panel includes the first lines generated from primary prostate cancer tissue, and also new lines from metastatic tissue. Critically, the lines retained salient features of the original patient tumors, including histopathology, clinical marker expression, chromosomal aberration and gene expression profiles. Furthermore, they span major histopathological and molecular subtypes of prostate cancer, capturing diverse inter- and intra-tumoral heterogeneity. Host castration led to the development of castrate-resistant tumors, including the first model of complete neuroendocrine transdifferentiation. This publicly-available resource provides novel tools to advance mechanistic understanding of disease progression and response to therapy, and delivers clinically-relevant model systems for evaluation of preclinical drug efficacy. 3 primary tumors and 21 xenograft tumors

2013-01-12 | E-GEOD-41188 | biostudies-arrayexpress

High fidelity patient-derived xenografts for accelerating prostate cancer discovery and drug development (expression)

2013-01-12 | E-GEOD-41192 | biostudies-arrayexpress

Epigenetic landscape of advanced prostate cancer

Project description:Prostate cancer is characterized as being histologically and molecularly heterogeneous. Additionally, epigenetic changes play an important role in regulating the progression of prostate cancer. However, epigenetic intraindividual heterogeneity is largely unknown in advanced prostate cancer. Hence, the epigenetic profiles of advanced prostate cancer, including autopsy cases, were investigated.

2024-07-20 | GSE256194 | GEO

Gene expression profiles (stroma and epithelium) of prostate cancer mouse models (JOCK1, Pro-Cat M-CM-^W JOCK1, Ubi-Cat M-CM-^W JOCK1)

Project description:The fibroblast growth factor receptor (FGFR) and canonical Wnt signaling pathways are important regulators of carcinogenesis; however, the interaction between these two pathways in the context of prostate cancer (PCa) has not been fully elucidated. Using novel transgenic mouse models, we describe Wnt-induced synergistic acceleration of FGFR1-driven adenocarcinoma; largely due to pronounced fibroblastic reactive stroma (RS) activation surrounding prostatic intraepithelial neoplasia (PIN) lesions in endogenous and reconstitution assays. Finally, both mouse and human RS are characterized by increases in TGF-M-NM-2 signaling heterogeneity immediately adjacent to PIN lesions; however, heterogeneity is lost during later stages of progression, likely contributing to tissue invasion. These studies confirm the importance of the FGFR1-Wnt-TGF-M-NM-2 signaling axes as driving forces behind reactive stroma and aggressive adenocarcinoma. To elucidate the mechanism behind the Wnt-accelerated FGFR1 adenocarcinoma, we performed laser capture microdissection (LCM) to separate pre-cancerous (hyperplasia and PIN) epithelia and adjacent reactive-stroma cells. We utilized frozen samples from specific time points (JOCK1, 40 weeks, Pro-Cat M-CM-^W JOCK1 and Ubi-Cat M-CM-^W JOCK1, 24 weeks) and performed gene expression profiling on the respective tissues.

2014-01-07 | E-GEOD-41344 | biostudies-arrayexpress

Transcription profiling by array of human stromal cells cultured with or without 3D BPH-1 prostate epithelial cells

Project description:BPH-1 prostate epithelial cells when cultured in Matrigel form 3D acini which closely recapitulate the tissue architecture of the prostate. The presence of primary stroma increases epithelial adhesions and causes changes in morphology. To identify the stromal signals which control actin/cadherin dynamics in epithelial cells we performed a microarray analysis on the stroma using Affymetrix U133 plus 2.0 arrays. Primary stroma from 7 different patients were cultured with (PSE) or without (PS) 3D BPH-1 epithelial acini to determine the gene expression changes within the stroma. The RNA from the Primary epithelia and stromal cultures were used at passages 1 or 1-3, respectively.

2010-06-09 | E-MEXP-2657 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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