CaArray_merco-00121: In silico dissection of cell-type-associated patterns of gene expression in prostate cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE82132 | GEO | 2016/06/02
SECONDARY ACCESSION(S): PRJNA324113
REPOSITORIES: GEO
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Project description:Prostate tumors are complex entities composed of malignant cells mixed and interacting with nonmalignant cells. However, molecular analyses by standard gene expression profiling are limited because spatial information and nontumor cell types are lost in sample preparation. We scored 88 prostate specimens for relative content of tumor, benign hyperplastic epithelium, stroma, and dilated cystic glands. The proportions of these cell types were then linked in silico to gene expression levels determined by microarray analysis, revealing unique cell-specific profiles. Gene expression differences for malignant and nonmalignant epithelial cells (tumor versus benign hyperplastic epithelium) could be identified without being confounded by contributions from stroma that dominate many samples or sacrificing possible paracrine influences. Cell-specific expression of selected genes was validated by immunohistochemistry and quantitative PCR. The results provide patterns of gene expression for these three lineages with relevance to pathogenetic, diagnostic, and therapeutic considerations. merco-00121 Assay Type: Gene Expression Provider: Affymetrix Array Designs: HG_U95Av2 Organism: Homo sapiens (ncbitax) Material Types: whole_orrganism, synthetic_RNA, organism_part, total_RNA Disease States: Normal, Prostate Cancer
2016-06-02 | E-GEOD-82132 | biostudies-arrayexpress
Project description:Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo.
2016-02-12 | GSE76456 | GEO
Project description:Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo. Agilent whole human genome aCGH oligonucleotide microarrays were used to assess copy number aberrations in 79 specimens from 20 patients as well as two pairs of cancer-associated fibroblasts (CAF) and benign/normal associated fibroblasts (NAF). 3 CAF/NAF sample pairs were also assessed for DNA copy number aberrations and copy-neutral LOH using the Infinium HumanOmniExpressExome BeadChip Kit.
2016-02-12 | E-GEOD-76456 | biostudies-arrayexpress
Project description:Although there are great differences between hyperplastic epithelium and stroma, so far, no data show differences in gene expression between epithelium and stroma, which may have a potential great impact on the discovery of drug targets We performed the microdissection and microarray to uncover the differences in gene expression between epithelium and stroma of the same patient with BPH
2021-09-08 | GSE183523 | GEO
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
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.
2009-09-05 | GSE17951 | GEO
Project description:Intronic and intergenic long noncoding RNAs (lncRNAs) are emerging gene expression regulators. The molecular pathogenesis of renal cell carcinoma (RCC) is still poorly understood, and in particular, limited studies are available for intronic lncRNAs expressed in RCC. Microarray experiments were performed with two different custom-designed arrays enriched with probes for lncRNAs mapping to intronic genomic regions. Samples from 18 primary clear cell RCC tumors and 11 nontumor adjacent matched tissues were analyzed with 4k-probes microarrays. Oligoarrays with 44k-probes were used to interrogate 17 RCC samples (14 clear cell, 2 papillary, 1 chromophobe subtypes) split into four pools. Meta-analyses were performed by taking the genomic coordinates of the RCC-expressed lncRNAs, and cross-referencing them with microarray expression data from three additional human tissues (normal liver, prostate tumor and kidney nontumor samples), and with large-scale public data for epigenetic regulatory marks and for evolutionarily conserved sequences. A signature of 29 intronic lncRNAs differentially expressed between RCC and nontumor samples was obtained (false discovery rate (FDR) <5%). An additional signature of 26 intronic lncRNAs significantly correlated with the RCC five-year patient survival outcome was identified (FDR <5%, p-value M-bM-^IM-$0.01). We identified 4303 intronic antisense lncRNAs expressed in RCC, of which 25% were cis correlated (r >|0.6|) with the expression of the mRNA in the same locus across three human tissues. Gene Ontology (GO) analysis of those loci pointed to M-bM-^@M-^Xregulation of biological processesM-bM-^@M-^Y as the main enriched category. A module map analysis of all expressed protein-coding genes in RCC that had a significant (r M-bM-^IM-%|0.8|) trans correlation with the 20% most abundant lncRNAs identified 35 relevant (p <0.05) GO sets. In addition, we determined that 60% of these lncRNAs are evolutionarily conserved. At the genomic loci containing the intronic RCC-expressed lncRNAs, a strong association (p <0.001) was found between their transcription start sites and genomic marks such as CpG islands and histones methylation and acetylation. Intronic antisense lncRNAs are widely expressed in RCC tumors. Some of them are significantly altered in RCC in comparison with nontumor samples. The majority of these lncRNAs is evolutionarily conserved and possibly modulated by epigenetic modifications. Our data suggest that these RCC lncRNAs may contribute to the complex network of regulatory RNAs playing a role in renal cell malignant transformation. This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-01-21 | E-GEOD-40914 | biostudies-arrayexpress
Project description:Advancing age is associated with substantial increases in the incidence rates of common diseases affecting the prostate including benign prostatic hyperplasia (BPH) and prostate carcinoma. However, to date, there is no established molecular explanation for the age-dependent increases in these pathologies. The prostate is comprised of a functional secretory epithelium supported by a spectrum of cell types and structural elements comprising the stroma. As reciprocal interactions between epithelium and stromal constituents are essential for normal organogenesis and serve to maintain normal functions, discordance within the stromal could permit or promote disease processes. In this study we sought to identify aging-associated alterations in the mouse prostate that could influence pathology. We quantitated transcript levels in microdissected periglandular stroma from young (4 month-old) and old (20-24 month-old) C57BL/6 mice, and identified a significant change in the expression of 1259 genes (p<0.05). These included increases in transcripts encoding genes associated with inflammation (e.g., Ccl8, Ccl12), genotoxic/ oxidative stress (e.g., Apod, Serpinb5) and paracrine-acting proteins (e.g., Cyr61). The expression of several collagen genes (e.g., Col1a1 and Col3a1) exhibited age associated declines. By immunofluorescence and electron microscopy we determined that the aged prostate contains an abundant disorganized collagen matrix and a significant increase in inflammatory infiltrates comprised of macrophages, T cells and, to a lesser extent, B cells. These findings demonstrated that during normal aging the prostate stroma exhibits phenotypic and molecular characteristics plausibly contributing to the striking age associated pathologies affecting the prostate through oxidative stress and inflammatory cell damage. Custom Agilent 44K whole mouse genome expression oligonucleotide microarrays as well as custom mouse cDNA microarrays were used to measure transcript levels in microdissected periglandular stroma from young (4 month-old) and old (20-24 month-old) C57BL/6 mice. All samples were laser-capture microdissected and total RNA isolated and amplified prior to hybridization against a reference pool of normal adult mouse tissues.
2010-09-15 | E-GEOD-21542 | biostudies-arrayexpress
Project description:Epithelial tumors can progress from a benign tissue overgrowth (hyperplasia) to a malignant neoplastic tumor, which is characterized by an increase in motility and invasiveness. The Cohen laboratory has developed an epithelial tumor model in which overexpression of the epidermal growth factor receptor gene (EGFR) leads to benign tissue hyperplasia. When combined with other cooperating factors, EGFR overexpression can lead to neoplasia and malignant metastasis. Microarray analysis were performed in normal epithelia, hyperplastic, and neoplastic tumors collected from Drosophila wing imaginal discs to identify genes whose misexpression correlates with tumor progression
2018-12-21 | GSE95613 | GEO
Project description:A data set of normal epithelium, serous ovarian surface epithelial-stromal tumors (benign and type II malignancies), stroma distal to tumor, and stroma adjacent to tumor (50 samples total). Additional cel files are included which represent replicate sampling from patients, and cel files that failed quality control but may be bioinformatically interesting. Additional replicate or failed cel files were not included in the final analysis (and so these samples were not included in the matrix). Background: Ovarian cancer is the most lethal gynecologic cancer in the United States. If caught in early stages, patient survival rate can reach 94%, when diagnosed at late stages survival rates drop to 28%. Correct diagnosis depends on the presence of definite symptoms: while ~90% of diagnosed ovarian cancers have symptoms, they tend to be unfocused and subacute. A definitive and early molecular signature of disease is thus desired. To further progress towards this goal, we present an Affymetrix™ human exon array data set measuring ovarian tumor expression, assembled using best practices. Method: Samples were collected from patients with benign and malignant (type II) serous ovarian surface epithelial-stromal tumors. Normal epithelium, tumor, stroma adjacent to tumor, and distal stroma were selected based on histopathology, and isolated using laser capture microdissection. Nugen products were used to perform random-primed mRNA amplification procedures (for full transcript capture) before hybridization to Affymetrix exon chips. Tumor expression and paracrine signaling was assessed using GC-RMA and a two-way Model I ANOVA. Single enrichment ontological analysis and gene network construction were performed to guide inferences about biological context. Results: In total, across 50 microarrays, ~270 million measurements were obtained. Based on comparisons to known ovarian cancer properties as established in molecular genetics literature, the initial analysis presented emphasizes data quality. Major trends between sample classes included: apical surface and tight junction activity, mitotic activity, benign tumor suppression, epithelial-mesenchymal transitioning, tumor oncogene activity, and paracrine signaling. A list of differentially expressed transcripts has been produced to enable rapid comparisons with published biomarker lists, but it is expected that detailed alternative transcript analysis will refine these predictions. Conclusions: A data set of 50 arrays, from carefully dissected serous ovarian surface epithelial-stromal tumors, has been produced, from which high quality measurements were obtained. While relatively small in number, this represents an important addition to the community pool of ovarian tumor samples, and the chosen platform enables bridging between 3' expression and exome sequencing data sets. This represents a significant contribution to the ovarian cancer genetics community. A total of 50 human ovary samples were used in analysis: 23 tissue samples laser capture microdissected from an ovary with a benign serous tumor (specifically 4 normal epithelium samples, 5 tumor samples, 6 stroma samples adjacent to the tumor, and 8 stroma samples distal of the tumor), and 27 tissue samples laser capture microdissected from an ovary with a malignant serous tumor (specifically 5 normal epithelium samples, 8 tumor samples, 7 stroma samples adjacent to the tumor, and 7 stroma samples distal of the tumor). Additional cel files were provided which, although were used in the quality control of the data set, were not used in the final experimental analysis. 8 replicates are included as cel files (1 from each cohort previously listed). 14 cel files were also included which failed quality control. Although the replicate and failed cel files were not used in the final analysis, they may still be interesting in other research.
2011-05-11 | E-GEOD-29156 | biostudies-arrayexpress