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Updated: Jun 24, 2025

A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
System analysis based on Anoikis-related genes identifies MAPK1 as a novel therapy target for osteosarcoma with
Zhouwei Wu1,2, Jiapei Yu1,2, Tao Han3,2
1Department of Orthopedics, the Second Affiliated Hospital, Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Background:
Osteosarcoma (OS) is the most common bone malignant tumor in children, and its prognosis is often poor. Anoikis is a unique mode of cell death.However, the effects of Anoikis in OS remain unexplored.
Method:
Differential analysis of Anoikis-related genes was performed based on the metastatic and non-metastatic groups. Then LASSO logistic regression and SVM-RFE algorithms were applied to screen out the characteristic genes. Later, Univariate and multivariate Cox regression was conducted to identify prognostic genes and further develop the Anoikis-based risk score. In addition, correlation analysis was performed to analyze the relationship between tumor microenvironment, drug sensitivity, and prognostic models.
Results:
We established novel Anoikis-related subgroups and developed a prognostic model based on three Anoikis-related genes (MAPK1, MYC, and EDIL3). The survival and ROC analysis results showed that the prognostic model was reliable. Besides, the results of single-cell sequencing analysis suggested that the three prognostic genes were closely related to immune cell infiltration. Subsequently, aberrant expression of two prognostic genes was identified in osteosarcoma cells. Nilotinib can promote the apoptosis of osteosarcoma cells and down-regulate the expression of MAPK1.
Conclusions:
We developed a novel Anoikis-related risk score model, which can assist clinicians in evaluating the prognosis of osteosarcoma patients in clinical practice. Analysis of the tumor immune microenvironment and chemotherapeutic drug sensitivity can provide necessary insights into subsequent mechanisms. MAPK1 may be a valuable therapeutic target for neoadjuvant chemotherapy in osteosarcoma.
Insights
We developed a new risk score model using Anoikis-related genes to predict osteosarcoma prognosis. This model aids clinicians and identifies MAPK1 as a potential therapeutic target for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genomics
Background:
- Osteosarcoma (OS) is a prevalent pediatric bone cancer with a poor prognosis.
- Anoikis, a mode of cell death, has unexplored roles in OS.
Purpose of the Study:
- To investigate the role of Anoikis-related genes in osteosarcoma.
- To develop a prognostic model for OS based on Anoikis-related genes.
- To explore the relationship between these genes, the tumor microenvironment, and drug sensitivity.
Main Methods:
- Differential gene expression analysis between metastatic and non-metastatic OS groups.
- Machine learning algorithms (LASSO, SVM-RFE) for gene selection.
- Cox regression for prognostic gene identification and risk score development.
- Correlation analysis with tumor microenvironment and drug sensitivity data.
Main Results:
- A novel prognostic model was developed using three Anoikis-related genes: MAPK1, MYC, and EDIL3.
- The model demonstrated reliability in survival and ROC analyses.
- Prognostic genes correlated with immune cell infiltration; aberrant expression of MAPK1 and MYC was observed in OS cells.
- Nilotinib showed potential to induce OS cell apoptosis and downregulate MAPK1.
Conclusions:
- A novel Anoikis-related risk score model can aid clinical prognosis assessment for osteosarcoma patients.
- Tumor immune microenvironment and drug sensitivity analyses offer insights into OS mechanisms.
- MAPK1 presents a potential therapeutic target for neoadjuvant chemotherapy in osteosarcoma.
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