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Updated: Aug 28, 2025
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Sphingolipid metabolism is associated with osteosarcoma metastasis and prognosis: Evidence from interaction analysis
Xinyue Hu1, Xin Zhou2, Jue Zhang2
1School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Background:
Metabolism is widely involved in the occurrence and development of cancer. However, its role in osteosarcoma (OS) has not been elucidated.
Methods:
The open-accessed data included in this study were downloaded from The Cancer Genome Atlas (TCGA) database (TARGET-OS project). All the analysis was performed in R environments.
Results:
Based on the single sample gene set enrichment analysis algorithm, we quantified 21 metabolism terms in OS patients. Among these, sphingolipid metabolism was upregulated in the metastatic OS tissue and associated with a worse prognosis, therefore aroused our interest and selected for further analysis. Our result showed that sphingolipid metabolism could activate the Notch signaling and angiogenesis pathway, which might be responsible for the metastasis ability and poor prognosis. A protein-protein interaction network was constructed to illustrate the interaction of the differentially expressed genes between high and low sphingolipid metabolism. Immune analysis showed that multiple immune terms were upregulated in patients with high sphingolipid metabolism activity. Then, a prognosis model was established based on the identified DEGs between patients with high and low sphingolipid metabolism, which showed great prediction efficiency. Pathway enrichment showed the pathway of myogenesis, spermatogenesis, peroxisome, KRAS signaling, pancreas beta cells, apical surface, MYC target, WNT beta-catenin signaling, late estrogen response and apical junction was significantly enriched in high risk patients. Moreover, we found that the model genes MAGEB1, NPIPA2, PLA2G4B and MAGEA3 could effectively indicate sphingolipid metabolism and risk group.
Conclusions:
In summary, our result showed that sphingolipid metabolism is associated with osteosarcoma metastasis and prognosis, which has the potential to be a therapeutic target for OS.
Insights
Sphingolipid metabolism is linked to osteosarcoma (OS) metastasis and poor prognosis. Targeting sphingolipid metabolism may offer a new therapeutic strategy for OS patients.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Metabolism plays a crucial role in cancer development.
- The specific role of metabolism in osteosarcoma (OS) remains largely unknown.
- This study investigates metabolic alterations in OS.
Purpose of the Study:
- To elucidate the role of sphingolipid metabolism in osteosarcoma (OS) progression and patient prognosis.
- To identify potential therapeutic targets for OS based on metabolic pathways.
Main Methods:
- Utilized The Cancer Genome Atlas (TCGA) database (TARGET-OS project) for data.
- Employed single-sample gene set enrichment analysis (ssGSEA) to quantify metabolic pathways.
- Constructed protein-protein interaction networks and developed a prognostic model.
Main Results:
- Sphingolipid metabolism was upregulated in metastatic OS and associated with worse prognosis.
- Sphingolipid metabolism activates Notch signaling and angiogenesis, potentially driving metastasis.
- A prognostic model based on differentially expressed genes showed high prediction efficiency.
Conclusions:
- Sphingolipid metabolism is significantly associated with osteosarcoma metastasis and prognosis.
- Sphingolipid metabolism represents a potential therapeutic target for osteosarcoma.
- Key genes (MAGEB1, NPIPA2, PLA2G4B, MAGEA3) indicate sphingolipid metabolism and risk status.
