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Updated: Sep 26, 2025
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Prediction and Identification of GPCRs Targeting for Drug Repurposing in Osteosarcoma
Manli Tan1, Shangzhi Gao2, Xiao Ru2
1Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Background:
Osteosarcoma (OS) is a malignant bone tumor common in children and adolescents. The 5-year survival rate is only 67-69% and there is an urgent need to explore novel drugs effective for the OS. G protein-coupled receptors (GPCRs) are the common drug targets and have been found to be associated with the OS, but have been seldom used in OS.
Methods:
The GPCRs were obtained from GPCRdb, and the GPCRs expression profile of the OS was downloaded from the UCSC Xena platform including clinical data. 10-GPCRs model signatures related to OS risk were identified by risk model analysis with R software. The predictive ability and pathological association of the signatures in OS were explored by bio-informatics analysis. The therapeutic effect of the target was investigated, followed by the investigation of the targeting drug by the colony formation experiment were.
Results:
We screened out 10 representative GPCRs from 50 GPCRs related to OS risk and established a 10-GPCRs prognostic model (with CCR4, HCRTR2, DRD2, HTR1A, GPR158, and GPR3 as protective factors, and HTR1E, OPN3, GRM4, and GPR144 as risk factors). We found that the low-risk group of the model was significantly associated with the higher survival probability, with the area under the curve (AUC) of the ROC greater than 0.9, conforming with the model. Moreover, both risk-score and metastasis were the independent risk factor of the OS, and the risk score was positively associated with the metastatic. Importantly, the CD8 T-cells were more aggregated in the low-risk group, in line with the predict survival rate of the model. Finally, we found that DRD2 was a novel target with approved drugs (cabergoline and bromocriptine), and preliminarily proved the therapeutic effects of the drugs on OS. These novel findings might facilitate the development of OS drugs.
Conclusion:
This study offers a satisfactory 10-GPCRs model signature to predict the OS prognostic, and based on the model signature, candidate targets with approved drugs were provided.
Insights
A novel prognostic model using 10 G protein-coupled receptors (GPCRs) effectively predicts osteosarcoma (OS) patient survival. This research identifies DRD2 as a potential therapeutic target, with existing drugs showing preliminary efficacy against OS.
Area of Science:
- Oncology
- Genomics
- Pharmacology
Background:
- Osteosarcoma (OS) is a prevalent bone cancer in children and adolescents with a concerning 5-year survival rate.
- Existing treatments for OS are limited, highlighting the urgent need for novel therapeutic strategies.
- G protein-coupled receptors (GPCRs) are implicated in OS but are underutilized as therapeutic targets.
Purpose of the Study:
- To develop a prognostic model for osteosarcoma (OS) based on G protein-coupled receptor (GPCR) expression.
- To identify novel therapeutic targets and potential drugs for OS treatment.
- To investigate the association between GPCR signatures, clinical outcomes, and immune cell infiltration in OS.
Main Methods:
- GPCR data sourced from GPCRdb and OS expression profiles from UCSC Xena.
- A 10-GPCR risk model was constructed using R software for OS prognosis.
- Bioinformatics analysis explored the predictive accuracy and pathological relevance of the GPCR signatures.
Main Results:
- A 10-GPCR prognostic model was established, with 6 protective and 4 risk factors.
- The model demonstrated high predictive accuracy (AUC > 0.9) and correlated with survival probability.
- DRD2 was identified as a druggable target, with cabergoline and bromocriptine showing preliminary therapeutic effects in OS.
Conclusions:
- The 10-GPCR model provides a robust signature for predicting OS prognosis.
- This study identifies potential therapeutic targets and repurposes existing drugs for OS treatment.
- Findings may accelerate the development of novel therapeutic strategies for osteosarcoma.
