MicroRNAs Associated with Metastatic Prostate Cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Yuzhuo Wang
PROVIDER: E-GEOD-28029 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:To identify genes with the potential target of differentially expressed miRNA in metastatic prostate cancer, we have employed whole genome microarray expression profiling. Transplantable metastatic versus a non-metastatic prostate cancer xenograft line, both derived from one patient’s primary cancer, were developed via sub-renal capsule grafting of cancer tissue into NOD/SCID mice. The same RNA samples from both lines were also used for miRNA sequencing. Overlapped genes of predicted targets of differentially expressed miRNAs and differentially expressed in microarray platform showed potential markers of combination of miRNA and gene in metastatic prostate cancer.
2012-03-11 | GSE28029 | GEO
Project description:Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen and the estrogen receptor, in synergy with androgen, are essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen plays in prostate carcinogenesis, and the precise mechanisms involved, remain unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor Beta (ERβ) agonist (genistein) and the inhibitory action of an anti-estrogen (ICI 182, 780) in patient-derived PCa xenograft models mimicking localized and metastatic disease. In this study, we compared the gene expression profiles of treated and untreated PCa xenografts using microarrays to identify a unique set of genes that were both up-regulated by genistein treatment and down-regulated by the anti-estrogen, ICI 182,780. Five of the six genes identified from this comparison belonged to the metallothionein (MT) gene family. Knock-down of ERβ led to a reduction in MT gene expression, confirming its role in regulating these genes. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumour lines, both of which were originally derived from the same PCa patient. Together our data provides evidence for the role of ERβ signalling in PCa metastasis and implicates estrogen-stimulated MT gene expression in this process. Three samples each (total RNA extracted from three tumours of three different animals from each group) for control, genistein and ICI were used for the array.
2012-12-27 | E-GEOD-43146 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by miRNA chip array, using Agilent-070156 Human_miRNA_V21.0_Microarray plateform. Results: Differential analysis showed the expressions of 27 EV delivered miRNAs were significantly different between serum of patients with bone-metastatic PCa and non-bone-metastatic PCa with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.
2020-01-31 | GSE134266 | GEO
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
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 22 xenograft tumors
2013-01-12 | E-GEOD-41192 | biostudies-arrayexpress
Project description:Background/Objective: MicroRNAs (miRNAs) play a pivotal role in cancerogenesis and cancer progression, but their specific role in metastasis of clear cell renal cell carcinomas (ccRCCs) as so-called metastamirs is still limited. Based on microRNA microarray analyses from normal (n=12) and cancerous (n=12) samples of ccRCC specimens and from bone metastases (n=9) of ccRCC patients, we identified a set of 57 differentially expressed microRNAs between those three sample groups of ccRCC. A selected panel of 33 miRNAs, including miRNAs reported in the literature as differentially expressed in non-metastatic RCC, was validated by RT-qPCR on 57 clinical samples. 30 of the 33 examined miRNAs were confirmed to be deregulated. A stepwise down-regulated miRNA expression from normal over primary tumor to metastatic tissue samples was found to be typical. 23 miRNAs (miR-10b/-19a/-19b/-20a/-29a/-29b/-29c/-100/-101/-126/-127/-130/-141/-143/-145/-148a/-192/-194/-200c/-210/-215/-370/-514) were down-regulated in metastatic tissue samples in comparison to normal tissue. This down-regulated expression in metastatic tissue was also present in 21 miRNAs except for miR-127 and miR-370. The altered miRNA profiles including the newly identified metastasis-associated miRNAs, the compiled predicted miRNA-target interactions, and the significant correlations of miRNAs which were either lost or newly appeared in the studied sample groups afford a solid basis for further functional analyses of individual miRNAs. In this study, microarray-based profiling was performed from 9 bone metastatic tissue samples from 9 patients with clear cell renal cell carcinoma (ccRCC). For controls, 2 bone metastatic samples from two patients with prostate carcinoma and 5 total RNA pools (2 different pools of total RNAs isolated from malignant renal tissue samples derived from different ccRCC patients; 1 pool from non-malignant renal tissue of ccRCC patients; 2 pools of total RNA both from malignant and non-malignant prostate cancer tissue) were used. In addition, matched malignant (e.g., malignant NC2) and non-malignant (e.g., non-malignant NN1) samples from two independent 12 ccRCC sets were profiled (these samples were previously analyzed on a different Platform in GSE12105). The 2002 TNM System and the 2004 WHO classification was used for staging and grading.
2013-02-26 | E-GEOD-37989 | biostudies-arrayexpress
Project description:Purpose: The goals of this study are to compare the serum extracellular vesicle (EV) delivered miRNA levels of patients with bone-metastatic prostate cancer (PCa), non-bone -metastatic PCa and benign prostatic hyperplasia (BPH), and to identify EV-delivered microRNAs in patient’s serum as indicators for bone-metastatic PCa. Methods:Serum extracellular vesicle delivered miRNA profiles of patients with bone-metastatic PCa or non-bone -metastatic PCa or BPH were generated by deep sequencing, using Illumina HiSeqTM 2500 platform Results: Using an optimized data analysis method, we mapped about 17 million sequence reads per sample. Differential analysis showed the expressions of 35 EV delivered miRNAs were significantly different between serum of patients with PCa and BPH, with a p value <0.05. the expressions of 5 EV delivered miRNAs were confirmed with qRT–PCR. Conclusions: Serum EV-delivered miR-181a-5p is a promising diagnostic biomarker for bone-metastatic PCa.
2020-01-31 | GSE134205 | GEO
Project description:Developing animal models representating the cancer biology of advanced prostate cancer patients is challenging but essential for delivering individualized medical therapies. In an effort to develop patient derived xenograft (PDX) models, we took the metastatic site tissue from the rib lesion twice (ie, before and after enzalutamide treatment) over a twelve week period and implanted subcutaneously and under the renal capsule in immuno-deficient mice. To characterize and compare the genome and transcriptome landscapes of patient tumor tissues and the corresponding PDX models, we performed whole exome and transcriptome sequencing for metastatic tumor tissue as well as its derived PDXs. We demonstrated the feasibility of developping PDX models from patient who developed castrate-resistant prostate cancer. Our data suggested PDX models preserve the patient’s genomic and transcriptomic alterations in high fidelity, as illustrated by somatic mutation, copy number variation, gene fusion and gene expression. RNA sequencing of prostate cancer tumor tissue and derived xenograft using Illumina HiSeq 2000.
2015-06-30 | E-GEOD-70380 | biostudies-arrayexpress
Project description:Metastatic prostate cancer (PCa) is a terminal disease and establishment of novel therapeutic strategy specifically targeting metastasis is critically required for its management. This study was aimed at identifying metastasis-driving genes which could potentially be therapeutic targets for metastatic prostate cancer. Integrative analysis of gene expression profiles from a pair of metastatic and non-metastatic prostate cancer tissue xenografts was used to identify potential prostate cancer metastasis-driving genes. Among the candidate genes found, GATA2, a master regulator gene in the development of hematopoietic system, was particularly interesting since it is an important pioneer factor in the regulation of AR-target gene in prostate cancer. In consistent with our finding, elevated expression of the GATA2 gene in metastatic prostate cancers was found and its expression was significantly correlated with poor prognosis in prostate cancer patients. Furthermore, indication of the GATA2 gene maybe the metastasis-driving gene was evidenced in decreased of cell migration, tissue invasion and focal adhesion disassembly in GATA2-down-regulated LNCaP cells. Global gene expression analysis after silencing of the GATA2 gene revealed a significant changed in cell transcriptomes with ~ 2500 genes with > 2 fold mRNA level changed and FDR <0.05, indicates that GATA2 plays a critical role in cell reprogramming as pioneer factor in the development of prostate cancer metastasis. LNCaP human prostate cancer cells transiently knockdown with siRNA that specifically targeting GATA2 (siGATA2) or scrambled siRNA (sicontrol). RNAs were isolated from cells after 72 hours of incubation. Gene expression profiles of four biological replicates from each sample group were analyzed to identify differentially regulated downstream genes after knockdown of GATA2.
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Project description:Samples of benign prostate tissue, localized prostate cancer tissue, and metastatic prostate cancer tissue are profiled to study expression changes in diagnosis and progression of prostate cancer. Each tissue sample is also profiled for metabolomics data Keywords: Cancer Progression 41 samples were analyzed (16 benign prostate tissue, 12 local prostate cancer tissue, 13 metastatic prostate cancer tissue)
2011-03-30 | E-GEOD-8511 | biostudies-arrayexpress