Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 26 unique pairs of biopsy and surgical resection specimens were profiled. Paired samples are denoted in the Sample 'characteristics' field.
Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 5 unique pairs of diagnostic biopsy and surgical resection specimens were profiled. Paired samples are denoted in the Sample 'characteristics' field.
Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 65 unique diagnostic biopsy specimens were profiled. Samples with paired surgical resection specimens (not included in this submission) are denoted in the Sample 'characteristics' field.
Project description:Osteosarcoma is a malignancy with variable outcomes that are not tightly aligned with chemotherapy response. Previous work has suggested a possible role for microRNAs (miRNAs) in determining the susceptibility of osteosarcomas to treatment but formal miRNA-based outcome models have not been reported. Formalin-fixed, paraffin-embedded (FFPE) specimens may be a unique approach for such studies in a rare malignancy. We used supervised principal components analysis and logistic regression to study survival and chemoresponse endpoints, and miRNA activity and gene set analysis algorithms to study miRNA regulatory networks using mRNA data. Our study also creates a paradigm for FFPE-based miRNA clinical biomarker research in rare tumors. 37 unique diagnostic biopsy specimens were profiled. Samples with paired surgical resection specimens (not included in this submission) are denoted in the Sample 'characteristics' field.
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.
Project description:Osteosarcoma is the most common primary malignant bone tumor in children. Validated markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At the tested loci, samples obtained from patients who experienced disease relapse were generally more methylated than those from patients who did not have recurrence. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and five year event-free survival, with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies. 15 samples. HpaII libraries were compared to at least 3 MspI libraries from the same sample
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).