Homo sapiens
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ABSTRACT:
PROVIDER: PRJNA146433 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Global gene expression analysis was performed on a panel of 23 osteosarcoma samples of primary and metastatic origin using the Applied Biosystems Gene Expression Array System. When comparing the primary tumours with the metastases, we found a significantly increased expression of genes involved in immunological processes, e.g. coding for cytokines and chemokines, in the metastatic samples, suggesting that these signal molecules play an important role in promoting metastasis. In addition, a comparison of the gene expression in primary samples from patients with or without metastases demonstrated that patients who later developed metastases had high expression of the chemokine (C-X-C motif) receptor 4 (CXCR4), similar to the metastatic samples. Increased knowledge of mechanisms and interactions between specified molecular signalling pathways in osteosarcomas could lead to a more rational strategy for development of targeted therapy.
2012-01-01 | GSE32981 | GEO
Project description:Global gene expression analysis was performed on a panel of 23 osteosarcoma samples of primary and metastatic origin using the Applied Biosystems Gene Expression Array System. When comparing the primary tumours with the metastases, we found a significantly increased expression of genes involved in immunological processes, e.g. coding for cytokines and chemokines, in the metastatic samples, suggesting that these signal molecules play an important role in promoting metastasis. In addition, a comparison of the gene expression in primary samples from patients with or without metastases demonstrated that patients who later developed metastases had high expression of the chemokine (C-X-C motif) receptor 4 (CXCR4), similar to the metastatic samples. Increased knowledge of mechanisms and interactions between specified molecular signalling pathways in osteosarcomas could lead to a more rational strategy for development of targeted therapy. Total RNA was isolated from tumor tissue of osteosarcoma patients. Gene expression patterns of metastatic versus primary samples were compared, as well as primary samples from patients who did or did not later develop metastases.
2012-01-01 | E-GEOD-32981 | biostudies-arrayexpress
Project description:We report that the cell of origin plays an important role in this metastatic tropism. Following injection into the arterial circulation of mice, each of the identically transformed cell types gave rise to different metastatic patterns. Using gene expression analysis, we identified the chemokine receptor CXCR4 as being instrumental in determining the distinct metastatic patterns between skeletal muscle precursor cells and skeletal myoblasts. 3 independent cell lines of primary human skeletal myoblasts, primary skeletal muscle cell precursors, and each of these cell lines transformed with hTERT, the early region of SV40 encoding T-Ag and t-Ag, and RasG12V analysis of primary human skeletal myoblasts, primary skeletal muscle cell precursors, and each of these cell lines transformed with hTERT, the early region of SV40 encoding T-Ag and t-Ag, and RasG12V
2016-02-13 | E-GEOD-19294 | biostudies-arrayexpress
Project description:In some types of cancer, telomere length is maintained by the Alternative Lengthening of Telomeres (ALT) mechanism. We characterized a series of high-grade osteosarcomas from 22 non-metastatic and non-pre-treated pediatric patients. Using the presence of circular partially single-stranded extrachromosomal C-rich telomeric repeat sequences (C-Circles) as an ALT marker, we found that 16 of the 22 high-grade osteosarcomas were ALT-positive. In order to find copy number alterations associated with ALT mechanims, we used comparative genomic hybridization (CGH).
2022-05-13 | E-MTAB-11747 | biostudies-arrayexpress
Project description:Most cancer deaths are caused by metastasis but understanding how metastatic cancers adapt from their origin tissues to their target tissues remains a fundamental challenge. Here, we ask if the gene expression of primary and metastatic tumors is more similar to their tissue of origin or to their target tissue. We analyzed the gene expression profiles of both paired and unpaired primary and metastatic tumor patient cohorts across multiple cancer types, studying single-cell and bulk RNA-seq data. To quantify the similarities between tumor samples and their normal, noncancerous origin and targeted tissues, we computed the Euclidean distance between their expression profiles, termed their transcriptomic distances, at the whole-genome and pathway levels. While the expression of most primary tumors is more similar to origin than to their target tissues, the expression patterns of metastases shift towards their target tissue. In specific cases, we chart the alterations occurring at the pathway level, pointing to key adaptive transcriptomic changes. Notably, our analysis indicates that primary cancers across several cancer types are primed for metastasis before the process begins. We further reproduce our findings using a new, unpublished RNA-seq data from colorectal cancer patients with liver metastases This first of its kind systematic analysis of the expression landscape of primary tumors and metastases with respect to their normal origin and target tissues provides a transcriptomic-wide view of cancer tumors adaptations to their metastatic niches
2024-10-21 | GSE245351 | GEO
Project description:Background: Fatal cancer is often the result of spread, or metastasis, of a cancer cell from the site of its origin to a distant anatomic site. While the metastatic process and the foreign environment of the metastatic site impact a tumorâ??s biology, we continue to determine therapy for patients based upon their cancerâ??s site of origin. We have performed an unbiased analysis across metastatic solid tumors from common primary sites to determine the molecular impact of the metastatic process on site-specific biology and to identify novel therapeutic strategies. Methods: Global gene expression was used as a biological phenotype to perform a top-down analysis of 96 metastatic human tumors. Laser capture microdissection, RNA amplification, and microarray analysis were used to measure the transcription patterns of malignant epithelial cells. Genes, multi-gene expression â??signaturesâ??, and pathways associated with site of origin (SOO) and site of metastases (SOM) were identified using established computational approaches. SOO and SOM expression signatures were validated on multiple, independent datasets comprising 1217 samples (1104 samples from GSE2109 (Expression Project for Oncology) and 113 samples from GSE12630 (Monzon FA, Lyons-Weiler M, Buturovic LJ, Rigl CT et al. Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. J Clin Oncol 2009 May 20;27(15):2503-8. PMID: 19332734). Reverse phase proteomics and in vitro tissue culture were used to validate associations between biological pathways, site of primary, and implicated therapeutic combinations. Findings: SOO has the dominant influence on solid tumor biology as samples segregate based upon their primary site during unsupervised hierarchical clustering. In addition, statistically significant associations are identified between single genes and pathways and each primary site investigated and SOO signatures for colon, breast, ovary, lung, and prostate cancers accurately identify primary site for independent samples of both local and metastatic tumors independent of degree of histological differentiation. The impact of SOM on tumor biology is evident as genes and pathways are significantly associated with metastatic site and SOM signatures can be generated but they are not strongly predictive when applied to localized tumors. Pathway analysis identified relatively increased expression of MYC, beta-catenin, and SRC gene sets in metastatic colorectal cancers which was confirmed with proteomic analysis of a sub-set of the original tumors. Within colorectal cancers, high SRC expression also correlates with predicted oxaliplatin sensitivity and the combination of an SRC inhibitor with oxaliplatin demonstrated synergy in three independent colorectal cancer cell lines. Interpretation: Our findings suggest that the complex alterations required for metastasis do not obscure the impact of a cancer cellâ??s origin. SOO signatures have the potential to be highly accurate diagnostic tools and the underlying site-specific biology can be used to identify novel therapeutic targets for advanced cancers. Keywords: Gene expression analysis Ninety-six laser capture microdissected adenocarcinoma patient tumor samples of various primary and metastatic sites were processed for Total RNA. Our 96-sample datatset was enriched by inclusion of previously deposited microarray data in GEO (reprocessed for this study): A total of 1217 samples (1104 samples from GSE2109, 113 samples from GSE12630) were reprocessed from the CEL files using RMA. Supplementary files: The reprocessed data matrices. A list of the 1217 Samples' GSM accession numbers and the corresponding reprocessed sample IDs.
2016-02-13 | E-GEOD-18549 | biostudies-arrayexpress
Project description:We report that the cell of origin plays an important role in this metastatic tropism. Following injection into the arterial circulation of mice, each of the identically transformed cell types gave rise to different metastatic patterns. Using gene expression analysis, we identified the chemokine receptor CXCR4 as being instrumental in determining the distinct metastatic patterns between skeletal muscle precursor cells and skeletal myoblasts.
2016-02-13 | GSE19294 | GEO
Project description:Osteosarcoma is a relatively rare solid tumour, but the most common primary bone cancer. It predominantly affects young people and is highly malignant, requiring aggressive surgical resection and cytotoxic chemotherapy. Five-year survival for patients with metastatic osteosarcoma is only around 30% 14. We report that pigs with heterozygous and homozygous inactivation of TP53 consistently develop osteosarcomas, providing a new model of osteosarcoma at human scale to understand and treat this devastating disease. Gene expression profiling and data analysis was further described in 'A porcine model of osteosarcoma' by Anja Saalfrank et al. (2016).
2016-02-23 | GSE78214 | GEO
Project description:Background: Fatal cancer is often the result of spread, or metastasis, of a cancer cell from the site of its origin to a distant anatomic site. While the metastatic process and the foreign environment of the metastatic site impact a tumor’s biology, we continue to determine therapy for patients based upon their cancer’s site of origin. We have performed an unbiased analysis across metastatic solid tumors from common primary sites to determine the molecular impact of the metastatic process on site-specific biology and to identify novel therapeutic strategies. Methods: Global gene expression was used as a biological phenotype to perform a top-down analysis of 96 metastatic human tumors. Laser capture microdissection, RNA amplification, and microarray analysis were used to measure the transcription patterns of malignant epithelial cells. Genes, multi-gene expression “signatures”, and pathways associated with site of origin (SOO) and site of metastases (SOM) were identified using established computational approaches. SOO and SOM expression signatures were validated on multiple, independent datasets comprising 1217 samples (1104 samples from GSE2109 (Expression Project for Oncology) and 113 samples from GSE12630 (Monzon FA, Lyons-Weiler M, Buturovic LJ, Rigl CT et al. Multicenter validation of a 1,550-gene expression profile for identification of tumor tissue of origin. J Clin Oncol 2009 May 20;27(15):2503-8. PMID: 19332734). Reverse phase proteomics and in vitro tissue culture were used to validate associations between biological pathways, site of primary, and implicated therapeutic combinations. Findings: SOO has the dominant influence on solid tumor biology as samples segregate based upon their primary site during unsupervised hierarchical clustering. In addition, statistically significant associations are identified between single genes and pathways and each primary site investigated and SOO signatures for colon, breast, ovary, lung, and prostate cancers accurately identify primary site for independent samples of both local and metastatic tumors independent of degree of histological differentiation. The impact of SOM on tumor biology is evident as genes and pathways are significantly associated with metastatic site and SOM signatures can be generated but they are not strongly predictive when applied to localized tumors. Pathway analysis identified relatively increased expression of MYC, beta-catenin, and SRC gene sets in metastatic colorectal cancers which was confirmed with proteomic analysis of a sub-set of the original tumors. Within colorectal cancers, high SRC expression also correlates with predicted oxaliplatin sensitivity and the combination of an SRC inhibitor with oxaliplatin demonstrated synergy in three independent colorectal cancer cell lines. Interpretation: Our findings suggest that the complex alterations required for metastasis do not obscure the impact of a cancer cell’s origin. SOO signatures have the potential to be highly accurate diagnostic tools and the underlying site-specific biology can be used to identify novel therapeutic targets for advanced cancers. Keywords: Gene expression analysis
2016-02-13 | GSE18549 | GEO