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Updated: Dec 10, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Exploring the association mechanism between metastatic osteosarcoma and non-metastatic osteosarcoma based on
1Department of Sports Medicine, Puai Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China.
Purpose:
Osteosarcoma (OS) is the primary malignant tumor which is common in children and adolescents. The treatment effect is still poor, though the treatment strategy has been dramatically improved.
Methods:
Differentially expressed genes in metastatic osteosarcoma and non-metastatic osteosarcoma were obtained first. Secondly, co-expression analysis has been processed for differentially expressed genes, and it is necessary to figure the gene drive of each module. Furthermore, both GO function and KEGG pathway enrichment analysis were performed on the module genes. Comprehensively, the module gene set which was predicted according to hypergeometric testing was importantly regulated by both transcription factors (TFs) and non-coding RNAs (ncRNAs).
Results:
Conclusively, 16 co-expression modules were obtained. ACAT1 and ATBF1 would actively regulate in dysfunction modules, and thus they are identified as osteosarcoma-driven genes. Enrichment results showed that the module genes were significantly involved in transcription factor activity, specific DNA binding of the RNA polymerase II proximal promoter sequence, DNA-binding transcriptional activator activity, ubiquitin-like protein transferase activity, and another biological process. Moreover, module genes significantly regulates FcγR-mediated phagocytosis, MAPK signaling pathway, phagocytosis, PI3K-Akt signaling pathway and others. Finally, we identified pivot ncRNAs (including CRNDE, miR-106a-5p, miR-181a-5p, etc) and pivot TFs (including NFKB1, STAT6, PPARG, RELA, etc) that significantly regulate dysfunction modules.
Conclusion:
Overall, this work deciphered a co-expression network of common core pathogenic genes including metastatic osteosarcoma and non-metastatic osteosarcoma. It helps to identify core dysfunction modules and potential regulatory factors of the disease and improves understanding the underlying molecular association mechanisms between the two diseases.
Insights
This study identifies key genes and regulatory factors in osteosarcoma (OS) by analyzing gene expression networks. The findings enhance understanding of molecular mechanisms driving OS progression and potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Bioinformatics
Background:
- Osteosarcoma (OS) is a primary bone cancer prevalent in children and adolescents.
- Despite treatment advancements, outcomes for OS, particularly metastatic forms, remain poor.
Purpose of the Study:
- To decipher the co-expression network of common core pathogenic genes in metastatic and non-metastatic osteosarcoma.
- To identify core dysfunction modules and potential regulatory factors (transcription factors and non-coding RNAs) in osteosarcoma.
Main Methods:
- Differential gene expression analysis between metastatic and non-metastatic osteosarcoma.
- Co-expression network construction and module identification.
- Gene Ontology (GO) and KEGG pathway enrichment analysis.
- Identification of regulatory transcription factors (TFs) and non-coding RNAs (ncRNAs).
Main Results:
- Sixteen co-expression modules were identified, with ACAT1 and ATBF1 highlighted as osteosarcoma-driven genes.
- Module genes are significantly enriched in transcription factor activity, DNA binding, and ubiquitin-like protein transferase activity.
- Key pathways regulated include FcγR-mediated phagocytosis, MAPK signaling, and PI3K-Akt signaling.
- Pivot ncRNAs (e.g., CRNDE, miR-106a-5p) and TFs (e.g., NFKB1, STAT6) regulating dysfunction modules were identified.
Conclusions:
- This study elucidates a co-expression network for osteosarcoma, revealing common pathogenic genes.
- Identified core dysfunction modules and regulatory factors provide insights into molecular mechanisms.
- Findings contribute to a better understanding of the molecular associations between different osteosarcoma subtypes.
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