In silico analyses of survival-associated microRNA signatures in pediatric osteosarcoma
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE79181 | GEO | 2016/03/22
SECONDARY ACCESSION(S): PRJNA315116
REPOSITORIES: GEO
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Project description:Osteosarcoma is the most common bone tumor in children, adolescents, and young adults. In contrast to other childhood malignancies, no biomarkers have been consistently identified as predictors of outcome. This study was conducted to assess the microRNAs (miRs) expression signatures in pre-treatment osteosarcoma specimens and correlate with outcome to identify biomarkers for disease relapse The cohort consisted of 25 patients of 70% Mexican-American ethnicity. High-throughput RT-qPCR approach was used to generate quantitative expression of 754 miRs in the human genome.
2016-03-22 | E-GEOD-79181 | biostudies-arrayexpress
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Project description:Osteosarcoma is the most common primary malignant tumour of bone occurring in children and young adolescents. Osteosarcoma is characterized by considerable phenotypic and genomic heterogeneity, and few recurrent targetable genetic changes have been reported. Osteosarcoma exhibits a complex karyotype with high genomic and chromosomal instability; and harbours multiple rearrangements across the genome, kataegis and chromothripsis as well as epigenetic changes. Here we have performed DNA methylation profiling on 10 osteosarcoma patient samples and four bones using the Infinium HumanMethylation450 BeadChip from Illumina, covering 485,000 CpG sites across the genome.
2022-01-31 | GSE161407 | GEO
Project description:Osteosarcoma is the most common malignancy of bone, and occurs most frequently in children and adolescents. Currently, the most reliable technique for prognostication is measuring histopathologic tumor necrosis following preoperative chemotherapy, and favourable prognosis is signified by 90% or greater estimated necrosis of the tumour. Neither genetic testing nor molecular biomarkers have been described for this tumour. We used the novel nanoString mRNA expression analysis system to analyzed total RNA from 35 flash-frozen sporadic paediatric osteosarcoma biopsy and resection specimens to quantify mRNA expression for 17 oncogenes and tumour suppressor genes. Three oncogenes, cell cycle regulator gene CDC5L, the RecQ DNA helicase gene RECQL4, and the cyclin-dependent kinase gene CDK4, were more highly expressed (p<0.05) in tumours which responded poorly to neoadjuvant chemotherapy. A similar trend (p<0.10) was identified for the osteoblast-specific transcription factor gene RUNX2. No statistically significant difference existed in comparing expression of CDC5L, RECQL4, CDK4, and RUNX2 between biopsy and resection samples. Additionally, analysis of expression data in the context of histological subtype yielded preliminary results for deducing molecular subtypes of osteosarcomas. Osteoblastic osteosarcomas possessed higher expression of CDKN1A, PTEN, and RUNX2 relative to their fibroblastic counterparts (p<0.05). This research study shows that CDC5L, RECQL4, and CDK4 tumour expression levels may be useful for identifying patients who may not benefit from the current standardized chemotherapy regimen. Total RNA was isolated from 52 pediatric osteosarcoma samples (prechemotherapy biopsies and resections), 3 osteosarcoma cell lines, and normal human osteoblasts. nanoString mRNA expression analysis was applied to samples split between 3 batches to compare samples based on clinical and pathologic data reports, and to compare samples with normal human osteoblasts. For 43 samples, there were complete data and the RNA was successfully assayed. Analysis was performed using R.
2016-03-15 | E-GEOD-45275 | biostudies-arrayexpress
Project description:Osteosarcoma (OS) is the most common primary malignant tumor of bone; it occurs most commonly in the metaphyseal regions of long bones in adolescents and young adults. Conventional osteosarcoma is characterized by complex karyotypes with a high degree of aneuploidy and numerous structural aberrations such as copy number alterations (CNAs) and genomic rearrangements. The data comprise of array copy number data (N=113) from pre-therapeutic osteosarcoma. These have been derived from Affymetrix CytoscanHD. The study searches for driver genes and examines cancer evolution. Note (added 8th June 2016): This experiment is extended in an experiment described under accession E-MTAB-4815. It contains data for 97 samples from this experiment are also included in E-MTAB-4815.
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Project description:Osteosarcoma is the most common malignancy of bone, and occurs most frequently in children and adolescents. Currently, the most reliable technique for prognostication is measuring histopathologic tumor necrosis following preoperative chemotherapy, and favourable prognosis is signified by 90% or greater estimated necrosis of the tumour. Neither genetic testing nor molecular biomarkers have been described for this tumour. We used the novel nanoString mRNA expression analysis system to analyzed total RNA from 35 flash-frozen sporadic paediatric osteosarcoma biopsy and resection specimens to quantify mRNA expression for 17 oncogenes and tumour suppressor genes. Three oncogenes, cell cycle regulator gene CDC5L, the RecQ DNA helicase gene RECQL4, and the cyclin-dependent kinase gene CDK4, were more highly expressed (p<0.05) in tumours which responded poorly to neoadjuvant chemotherapy. A similar trend (p<0.10) was identified for the osteoblast-specific transcription factor gene RUNX2. No statistically significant difference existed in comparing expression of CDC5L, RECQL4, CDK4, and RUNX2 between biopsy and resection samples. Additionally, analysis of expression data in the context of histological subtype yielded preliminary results for deducing molecular subtypes of osteosarcomas. Osteoblastic osteosarcomas possessed higher expression of CDKN1A, PTEN, and RUNX2 relative to their fibroblastic counterparts (p<0.05). This research study shows that CDC5L, RECQL4, and CDK4 tumour expression levels may be useful for identifying patients who may not benefit from the current standardized chemotherapy regimen.
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Project description:Osteosarcoma (OS)is a rare primary malignant bone tumor in adolescents and children with a poor prognosis. Identification of prognostic genes lags far behind the advance of the treatments. We identified differential genes by microarray analysis from paired OS tissues. Hub genes, gene set enrichment analysis, and pathway analysis were performed to gain an insight into the pathway alterations of OS. These results showed CPE could be served as a prognostic factor in osteoblastic OS and should be further investigated as potential therapeutic target. The present study evaluated the whole transcriptome expression of osteosarcoma progression and provided novel therapeutic targets for advanced osteosarcoma.
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Project description:Osteosarcoma (OS) is the most common primary malignant tumor of bone; it occurs most commonly in the metaphyseal regions of long bones in adolescents and young adults. Conventional osteosarcoma is characterized by complex karyotypes with a high degree of aneuploidy and numerous structural aberrations such as copy number alterations (CNAs) and genomic rearrangements. We characterized the landscape of somatic copy number alterations (SCNAs) in a large cohort (n=160) of osteosarcoma (OS) samples using the whole-genome CytoScan High Density arrays. This experiment is an extension of E-MTAB-3998. It contains data for 97 samples that is also included in E-MTAB-3998. The samples derived from E-MTAB-3998 identified using the 'Description' field in the sample attributes.
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Project description:Aberrations in the Hedgehog (Hh) pathway are known to related to several malignancies. However, little is known about the function of GLI2, a transcription factor in the Hh pathway, in osteosarcoma. Osteosarcoma is the most frequent primary bone sarcoma in children and adolescents. Despite survival rates of osteosarcoma patients have increased, the prognosis of patients with metastasis remains poor. Therefore, the development of novel therapeutic strategies for osteosarcoma patients is development of novel therapeutic strategies for osteosarcoma patients is urgently needed. Aberrations in the Hedgehog (Hh) pathway are known to related to several malignancies. However, little is known about the function of GLI2, a transcription factor in the Hh pathway, in osteosarcoma. Our findings revealed that GLI2 was overexpressed in osteosarcoma tissues. Additionally, GLI2 is involved in the metastasis of osteosarcoma cells through the regulation of ribosomal protein S3 expression. Furthermore, we showed that arsenic trioxide (ATO) suppressed the invasion and lung metastasis of osteosarcoma cells by the inhibition of GLI transcription. Consequently, these finding reveal a novel function of GLI2 in the metastasis of osteosarcoma and that ATO may be a new therapeutic agentay be a new therapeutic agent. We revealed that a novel function of GLI2 in the metastasis of osteosarcoma and that ATO may be a new therapeutic agent for preventing osteosarcoma metastasis. Negative siRNA(U-2OS) and GLI2 siRNA(U-2OS)
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