RNA-Sequencing Predicts a Role of Androgen Receptor and Aldehyde Dehydrogenase 1A1 in Osteosarcoma Lung Metastases
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE220538 | GEO | 2023/08/01
REPOSITORIES: GEO
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Project description:Osteosarcoma (OS) is the most frequent malignant bone tumor with a high propensity for metastases. Through the tissue-specific alteration of p53 status, we have developed a genetically engineered mouse model of localized and metastatic OS. Gene expression analysis revealed naked cuticle homolog 2 (NKD2), a negative regulator of the Wnt signaling pathway, to be significantly downregulated in metastatic OS. An assessment of human OS tumors revealed downregulation of NKD2 in metastatic and recurrent OS. We determined that downregulation was secondary to methylation of the NKD2 promoter region for both mouse and human tumors. Furthermore, in vivo investigations indicate that NKD2 overexpression significantly diminishes OS tumor growth and metastasis and small molecule Wnt inhibitors can decrease OS growth and metastatic potential.
2015-03-12 | GSE43281 | GEO
Project description:Osteosarcoma (OS) is the most common primary bone tumour in children and young adults, and the second highest cause of cancer-related death in this age group. In spite of aggressive chemotherapy, disease-free survival has not improved significantly in the past 20 years, and 50% of patients subsequently develop fatal pulmonary metastasis. We have performed gene expression profiling of primary osteosarcoma biopsies (i) to identify prognostic markers, and (ii) to identify novel therapeutic targets. Keywords: Comaprison between disease status (metastatic vs non-metastatic) and normal
2010-08-30 | GSE9508 | GEO
Project description:Osteosarcoma (OS) is a primary malignant bone tumor commonly affecting children, adolescents, and young adults with a potential to metastasize to distal sites, most commonly lung. Here, we mapped the active chromatin landscapes of OS patients with varying extent of disease. We integrated histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) of OS tumors from four different diseased states to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary tumors that undergo metastasis (primary mets) have a distinct enhancer landscape compared to primary tumors that remain localized (localized) during the course of disease. The difference in chromatin activity shapes the transcriptional profile of OS patients. Some of the genes like PPP1R1B, PREX1 and IGF2BP1 whose role in OS pathogenesis and metastasis remains poorly understood, exhibit increased enhancer activity in primary mets along with higher RNA levels. Genome-wide loss-of-function screens also reveal these genes to be as selective dependencies in bone sarcomas, making them promising candidates for further investigation. Overall, differential chromatin activity in primary mets occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and migration process suggestive of their role in facilitating OS metastasis. Thus, this data demonstrates that metastatic potential is intrinsically present in primary mets OS much before the occurrence of metastasis and when the cells are presented with favorable conditions to migrate and colonize at a distant site, they under undergo metastasis.
2023-12-09 | GSE234998 | GEO
Project description:Osteosarcoma (OS) is a primary malignant bone tumor commonly affecting children, adolescents, and young adults with a potential to metastasize to distal sites, most commonly lung. Here, we mapped the active chromatin landscapes of OS patients with varying extent of disease. We integrated histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) of OS tumors from four different diseased states to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary tumors that undergo metastasis (primary mets) have a distinct enhancer landscape compared to primary tumors that remain localized (localized) during the course of disease. The difference in chromatin activity shapes the transcriptional profile of OS patients. Some of the genes like PPP1R1B, PREX1 and IGF2BP1 whose role in OS pathogenesis and metastasis remains poorly understood, exhibit increased enhancer activity in primary mets along with higher RNA levels. Genome-wide loss-of-function screens also reveal these genes to be as selective dependencies in bone sarcomas, making them promising candidates for further investigation. Overall, differential chromatin activity in primary mets occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and migration process suggestive of their role in facilitating OS metastasis. Thus, this data demonstrates that metastatic potential is intrinsically present in primary mets OS much before the occurrence of metastasis and when the cells are presented with favorable conditions to migrate and colonize at a distant site, they under undergo metastasis.
2023-12-09 | GSE234997 | GEO
Project description:Osteosarcoma (OS) is a primary malignant bone tumor commonly affecting children, adolescents, and young adults with a potential to metastasize to distal sites, most commonly lung. Here, we mapped the active chromatin landscapes of OS patients with varying extent of disease. We integrated histone H3 lysine acetylated chromatin (H3K27ac) profiles (n=13), chromatin accessibility profiles (n=11) and gene expression (n=13) of OS tumors from four different diseased states to understand the differences in their active chromatin profiles and its impact on molecular mechanisms driving the malignant phenotypes. Primary tumors that undergo metastasis (primary mets) have a distinct enhancer landscape compared to primary tumors that remain localized (localized) during the course of disease. The difference in chromatin activity shapes the transcriptional profile of OS patients. Some of the genes like PPP1R1B, PREX1 and IGF2BP1 whose role in OS pathogenesis and metastasis remains poorly understood, exhibit increased enhancer activity in primary mets along with higher RNA levels. Genome-wide loss-of-function screens also reveal these genes to be as selective dependencies in bone sarcomas, making them promising candidates for further investigation. Overall, differential chromatin activity in primary mets occurs in proximity of genes regulating actin cytoskeleton organization, cellular adhesion, and migration process suggestive of their role in facilitating OS metastasis. Thus, this data demonstrates that metastatic potential is intrinsically present in primary mets OS much before the occurrence of metastasis and when the cells are presented with favorable conditions to migrate and colonize at a distant site, they under undergo metastasis.
2023-12-09 | GSE234996 | GEO
Project description:Osteosarcoma (OS) is the most common primary bone tumour in children and young adults, and the second highest cause of cancer-related death in this age group. In spite of aggressive chemotherapy, disease-free survival has not improved significantly in the past 20 years, and 50% of patients subsequently develop fatal pulmonary metastasis. We have performed gene expression profiling of primary osteosarcoma biopsies (i) to identify prognostic markers, and (ii) to identify novel therapeutic targets. Keywords: Comaprison between disease status (metastatic vs non-metastatic) and normal Two-colour experiment. 7 samples for non-metastatic patients, 6 of which are analyzed in duplicate (dye-swaps); 11 samples for metastatic patients, 10 of which are analyzed in duplicate (dye-swaps); 5 samples of non-malignant bone analyzed individualy, no dye-swaps (i.e. 5 biological replicates).
2010-08-30 | E-GEOD-9508 | biostudies-arrayexpress
Project description:We used single-cell RNA sequencing to characterize the heterogeneity of circulating leukocytes in dogs, then employed the dataset to investigate how primary osteosarcoma (OS) tumors impacted circulating leukocytes.
2023-04-25 | GSE225599 | GEO
Project description:Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20-30%. T cell checkpoint blockade immunotherapies have revolutionized cancer treatment in the last decade, but their impact remains limited in osteosarcoma. In order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterization of a unique sample set comprising multiple osteosarcoma samples from seven patients, collected throughout the progression of the disease. We performed RNA-sequencing and imaging mass cytometry analysis on those samples to reveal the immunological landscape during osteosarcoma progression. Transcriptional and phenotypical hallmarks of cytotoxic T cell-driven anti-cancer immunity were enriched in metastatic lesions as compared to primary tumors. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly MAGEA-related antigens, in osteosarcoma metastases. Their overexpression in metastatic lesions was confirmed at protein level and positive expression of MAGEA3 in primary tumors showed a significant association with metastasis free survival. Importantly, we demonstrated the presentation of MAGE-derived peptides in three osteosarcoma cell lines. These findings indicate a concurrent augmentation of cytotoxic anti-tumor immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation warrants the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.
2024-02-07 | GSE237033 | GEO
Project description:In this study, we aimed to refine our understanding of the molecular events associated with the proteomic response to hypoxia in OS cells with different anatomic origins, namely from a primary and metastatic site. There are similarities in biology and treatment of OS in human and canine. We opted to use a canine parental osteosarcoma cell line (POS), which was cultured from a primary canine tumor24; and a highly metastatic POS cell line (HMPOS) that was derived from pulmonary metastatic lesions in mouse POS xenografts. We have chosen a protein-centric study design that combines 1) initially a label-free data dependent acquisition (DDA) method for enabling quantification of larger sets of proteins and global assessment of adaptive responses induced by hypoxia, 2) selection of hypoxia-responsive protein targets and 3) using parallel reaction monitoring (PRM) for quantitative monitoring of signature peptides of hypoxia-responsive protein targets to determine their precise response to hypoxia and to confirm hypoxia-regulated pathways. Functional biochemical assays provide additional validation of the proteomic findings. Taken together, our results describe the hypoxia response of OS cell phenotypes by inducing comprehensive alterations in the proteome biology that are associated with metabolic reprogramming, redox modulation and extra cellular matrix (EMC) remodeling.
2020-05-26 | PXD008986 | Pride
Project description:The expression profile of primary pediatric Ewing sarcoma (ES) and osteosarcoma (OS) were analyzed.
2016-01-03 | GSE73166 | GEO