Transcriptome analysis of primary normal fibroblasts and matched cancer associated fibroblasts
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE196354 | GEO | 2022/12/09
REPOSITORIES: GEO
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Project description:To understand the driving mechanisms for CAF activation, we performed H3K27ac and H3K4me1 Cleavage Under Targets and Tagmentation (CUT&Tag) analysis in six pairs of NFs and CAFs. At H3K4me1+ sites, we identified 3,333 regions with H3K27ac levels in CAFs ≥ 2-fold than matched NFs in more than 3 pairs, and defined them as CAF-activated enhancers.
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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. Methylation profiles of 5 pairs of were included in a molecular characterization of NSCLC fibroblast cell lines (CAFs) vs. normal lung fibroblasts (NFs). Methylation profiles of 5 paired primary NSCLC fibroblast cell lines (CAFs) and normal lung fibroblasts (NFs) were generated. Genes were determined to be hyper- and hypo-methylated based on paired analysis.
2011-04-08 | E-GEOD-27284 | biostudies-arrayexpress
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. Genotyping profiles of 4 pairs of were included in a molecular characterization of NSCLC fibroblast cell lines (CAFs) vs. normal lung fibroblasts (NFs). Genotyping profiles of 4 paired primary NSCLC fibroblast cell lines (CAFs) and normal lung fibroblasts (NFs) were generated. CNV was assessed using paired analysis.
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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. 30 samples: 15 primary NSCLC fibroblast cell lines, 15 normal lung fibroblast cell lines
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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. 30 samples: 15 primary lung tumor stroma, 15 normal lung parenchyma
2011-04-08 | E-GEOD-22863 | biostudies-arrayexpress
Project description:To identify miRNA differentially expressed in CAFs vs matched NFs and analyze the heterogeneity of miRNA expression profiles in the two kinds of cells, we established primary cultures of CAFs and paired NFs from six resected breast tumor tissue without any radiotherapy and chemotherapy treatment. Paired CAFs and NFs from six primary human breast carcinoma specimens were cultured,the third passage of primary cells was used in the experiments.
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Project description:Although how CAFs impact the tumor epithelium is being progressively unveiled, transcriptional processes of lineage plasticity in fibroblasts govern the acquisition and transition of the CAF phenotype are much less understood. Here, to explore the potential involvement of the circular RNAs (circRNAs) in fibroblast activation and phenotype acquisition, we isolated CAFs and NFs from human pancreatic cancer and paired normal pancreatic tissue. Next, we conducted circRNA profiling five CAFs and three paired NFs by high throughput sequencing. Our results showed that clusters of circRNAs were aberrantly expressed in CAFs compared with NFs, and provided potential targets for future treatment of PDAC and novel insights into PDAC microenvironment.
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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. Methylation profiles of 5 pairs of were included in a molecular characterization of NSCLC fibroblast cell lines (CAFs) vs. normal lung fibroblasts (NFs).
2011-04-08 | GSE27284 | 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]
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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. Genotyping profiles of 4 pairs of were included in a molecular characterization of NSCLC fibroblast cell lines (CAFs) vs. normal lung fibroblasts (NFs).
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