Homo sapiens
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PROVIDER: PRJNA283907 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetic changes through altered DNA methylation have been implicated with critical aspects of tumor progression, and have been extensively studied in cancer cells and tumor tissue samples. In contrast, our current knowledge of the aberrant genomic methylation in tumor-associated fibroblasts (TAFs), which are critical co-conspirators of tumor progression, is very scarce. To address this gap of knowledge, we conducted genome-wide DNA methylation profiling on lung TAFs and paired control fibroblasts (CFs) from surgical non-small cell lung cancer patients. We found widespread DNA hypomethylation concomitant with focal gains of DNA methylation in TAFs compared to CFs. The aberrant DNA methylation landscape of TAFs had a global impact on gene expression and a selective impact on the TGF-β pathway. The latter included hypermethylation-associated SMAD3 silencing, which was associated with a hyperresponsiveness to exogenous TGF-β1 in terms of contractility and extracellular matrix expression. In turn, activation of CFs with exogenous TGF-β1 partially mimicked the epigenetic alterations observed in TAFs, suggesting that TGF-β1 may be necessary but not sufficient to elicit such alterations. In addition, pathway enrichment analysis of the DNA methylation alterations revealed that a fraction of TAFs may be bone marrow-derived fibrocytes. Finally, survival analyses using DNA methylation and gene expression datasets identified aberrant DNA methylation on the EDARADD promoter sequence as a prognostic factor in NSCLC patients. Our findings shed light on the unique origin and molecular alterations underlying the aberrant phenotype of lung TAFs, and identify a stromal biomarker with potential clinical relevance.
2015-10-13 | GSE68851 | GEO
Project description:The tumor microenvironment strongly influences cancer development, progression and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC. We demonstrate that CAFs have greater ability than NFs to enhance the tumorigenicity of lung cancer cell lines. Microarray gene expression analysis of the 15 matched CAF and NF cell lines identified 46 differentially expressed genes, encoding for proteins that are significantly enriched for extracellular proteins regulated by the TGF-beta signaling pathway. We have identified a subset of 11 genes that formed a prognostic gene expression signature, which was validated in multiple independent NSCLC microarray datasets. Functional annotation using protein-protein interaction analyses of these and published cancer stroma-associated gene expression changes revealed prominent involvement of the focal adhesion and MAPK signalling pathways. Fourteen (30%) of the 46 genes also were differentially expressed in laser-capture micro-dissected corresponding primary tumor stroma compared to the matched normal lung. Six of these 14 genes could be induced by TGF-beta1 in NF. The results establish the prognostic impact of CAF-associated gene expression changes in NSCLC patients. This SuperSeries is composed of the following subset Series: GSE22862: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [expression profiling_CAFs] GSE22863: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [expression profiling_NSCLC stroma] GSE27284: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [methylation profiling] GSE27289: Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [genome variation profiling]
2011-04-08 | E-GEOD-22874 | biostudies-arrayexpress
Project description:Using paired tumor and non-tumor lung tissues from 47 individuals we identified common changes in DNA methylation associated with the development of non-small cell lung cancer. Pathologically normal lung tissue taken at the time of cancer resection was matched to tumorous lung tissue and together were probed for methylation status using Illumina GoldenGate arrays. For each matched pair the change in methylation at each CpG was calculated (the odds ratio), and these ratios were averaged across individuals and ranked by magnitude to identify the CpGM-bM-^@M-^Ys with the greatest change in methylation associated with tumor development. Using paired tumor and non-tumor lung tissues from 47 individuals we identified common changes in DNA methylation associated with the development of non-small cell lung cancer. Pathologically normal lung tissue taken at the time of cancer resection was matched to tumorous lung tissue and together were probed for methylation status using Illumina GoldenGate arrays. For each matched pair the change in methylation at each CpG was calculated (the odds ratio), and these ratios were averaged across individuals and ranked by magnitude to identify the CpGM-bM-^@M-^Ys with the greatest change in methylation associated with tumor development.
2012-07-02 | E-GEOD-27902 | biostudies-arrayexpress
Project description:Genome wide DNA methylation profiling of brain metastasis from colorectal and lung cancer. The Illumina Infinium MethylationEPIC was used to obtain DNA methylation profiles across approximately 850,000 CpGs in brain metastasis samples. Samples included 1 breast ductal invasive carcinoma, 4 colon adenocarcinoma, 1 melanoma, 1 multiple mieloma, 7 non small cell lung cancer adenocarcinoma, 3 non small cell lung cancer G3, 4 non small cell lung cancer SCC, 1 prostate cancer adenocarcinoma and 1 serous carcinoma.
2023-12-17 | GSE249157 | GEO
Project description:Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms including DNA methylation, have the potential to mediate the interactions between an individual?s genetics and environmental exposure. DNA methylation is highly cell type specific and individual cell type studies of DNA methylation in COPD are sparse. Fibroblasts are present within the airway and parenchyma of the lung and contribute to the aberrant deposition of extracellular matrix in COPD. No assessment or comparison of genome-wide DNA methylation profiles in airway and parenchymal fibroblasts from individuals with and without COPD has been undertaken. These data provide valuable insight into the molecular mechanisms contributing to COPD and the differing pathologies of small airways disease and emphysema in COPD. Methods: Genome-wide DNA methylation was evaluated at over 485,000 CpG sites using the Illumina Infinium HumanMethylation450 BeadChip array in airway (non-COPD n=8, COPD n=7) and parenchymal fibroblasts (non-COPD n=18, COPD n=28) isolated from individuals with and without COPD. Targeted gene expression was assessed by qPCR in matched RNA samples. Results: Differentially methylated DNA regions were identified between cells isolated from individuals with and without COPD in both airway and parenchymal fibroblasts. Only in parenchymal fibroblasts was differential DNA methylation associated with differential gene expression. A second analysis of differential DNA methylation variability identified 359 individual differentially variable CpG sites in parenchymal fibroblasts. No differentially variable CpG sites were identified in airway fibroblasts. Five differentially variable methylated CpG sites, associated with three genes were subsequently assessed for gene expression differences. Two genes (OAT and GRIK2) displayed significantly increased gene expression in cells isolated from individuals with COPD. Conclusions: Differential and variable DNA methylation was associated with COPD status in parenchymal fibroblasts but not airway fibroblasts. Aberrant DNA methylation was associated with altered gene expression imparting biological function to DNA methylation changes. Changes in DNA methylation are therefore implicated in the molecular mechanisms underlying COPD pathogenesis and may represent novel therapeutic targets.
2018-03-06 | GSE111396 | GEO
Project description:Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. Here, we report that most of lung cancer cell lines tested expressed predominantly ∆DNMT3B-del whereas normal bronchial epithelial cells expressed equal quantities of ∆DNMT3B and ∆DNMT3B-del. We demonstrate biological impacts of ∆DNMT3B4-del, a ∆DNMT3B-del isoform, in a transgenic mouse model. Expression of ∆DNMT3B4-del in the mouse lungs resulted in an increased global DNA hypomethylation, focal DNA hypermethylation, epithelial hyperplastia and tumor formation when challenged with a tobacco carcinogen. In patients with non-small cell lung cancer, 83% of the primary tumors expressed predominantly ∆DNMT3B-del. Our results demonstrate ∆DNMT3B4-del as a critical factor in developing aberrant DNA methylation during lung tumorigenesis.
2017-02-09 | GSE68922 | GEO
Project description:Gene expression signatures of cancer-associated fibroblasts in non-small cell lung cancer
| PRJNA1021183 | ENA
Project description:Global loss of DNA methylation and locus/gene-specific gain of DNA methylation are two distinct hallmarks of carcinogenesis. Aberrant DNA methylation is implicated in smoking-related lung cancer. In this study, we have comprehensively investigated the modulation of DNA methylation consequent to chronic exposure to a prototype smoke-derived carcinogen, benzo[a]pyrene diol epoxide (B[a]PDE), in genomic regions of significance in lung cancer, in normal human cells. We have used a pulldown assay for enrichment of the CpG methylated fraction of cellular DNA combined with microarray platforms, followed by extensive validation through conventional bisulfite-based analysis. Here, we demonstrate strikingly similar patterns of DNA methylation in non-transformed B[a]PDE-treated cells vs control using high-throughput microarray-based DNA methylation profiling confirmed by conventional bisulfite-based DNA methylation analysis. The absence of aberrant DNA methylation in our model system within a timeframe that precedes cellular transformation suggests that following carcinogen exposure, other as yet unknown factors (secondary to carcinogen treatment) may help initiate global loss of DNA methylation and region-specific gain of DNA methylation, which can, in turn, contribute to lung cancer development. Unveiling the initiating events that cause aberrant DNA methylation in lung cancer has tremendous public health relevance, as it can help define future strategies for early detection and prevention of this highly lethal disease. Methylated fragments in genomic DNA extracted from benzo[a]pyrene diol epoxide (B[a]PDE)-treated normal human fibroblasts versus control (solvent [dimethylsulfoxide (DMSO)-treated counterpart cells] were enriched with the MIRA assay and hybridized together with input genomic DNA to NimbleGen's whole genome tiling array.
2010-04-29 | E-GEOD-21532 | biostudies-arrayexpress
Project description:Prognostic Gene Expression Signature of Carcinoma Associated Fibroblasts in Non-Small Cell Lung Cancer [methylation profiling]
| PRJNA137327 | ENA
Project description:Cancer cell phenotypes are partially determined by epigenetic specifications such as DNA methylation. Metastasis development is a late event in cancerogenesis and might be associated with epigenetic alterations. Here, we analyzed genome wide DNA methylation changes that were associated with pro-metastatic phenotypes in non-small cell lung cancer using the Illumina HumanMethylation27 BeadChip platform.
2013-12-18 | GSE52144 | GEO