Comprehensive analysis of angiogenesis pattern and related immune landscape for individual treatment in osteosarcoma

by Selleckchem | Jan 01 2024

Postoperative recurrence and metastasis are the main reasons for the poor prognosis of osteosarcoma (OS). Currently, an ideal predictor for not only prognosis but also drug sensitivity and immunotherapy responses in OS patients is urgently needed. Angiogenesis plays a crucial role in tumour progression, which suggests its immense potential for predicting prognosis and responses to immunotherapy for OS. Angiogenesis patterns in OS were explored in depth in this study to construct a prognostic model called ANGscore and clarify the underlying mechanism involved in the immune microenvironment. The efficacy and robustness of the model were validated in multiple datasets, including bulk RNA-seq datasets (TARGET-OS, GSE21257), a single-cell RNA-seq dataset (GSE152048) and immunotherapy-related datasets (GSE91061, GSE173839). OS patients with a high ANGscore had a worse prognosis, accompanied by the immune desert phenotype. Pseudotime and cellular communication analyses in scRNA-seq data revealed that as the ANGscore increased, the malignant degree of cells increased, and IFN-γ signalling was involved in tumour progression and regulation of the tumour immune microenvironment. Furthermore, the ANGscore was associated with immune cell infiltration and the response rate to immunotherapy. OS patients with high ANGscore might be resistant to uprosertib, and be sensitive to VE821, AZD6738 and BMS.345541. In conclusion, we established a novel ANGscore system by comprehensively analysing the expression pattern of angiogenesis genes, which can accurately differentiate the prognosis and immune characteristics of OS populations. Additionally, the ANGscore can be used for patient stratification during immunotherapy, and guide individualized treatment strategies.

Comments:

The ANGscore sounds incredibly promising in addressing the challenges surrounding osteosarcoma (OS) prognosis and treatment. The integration of angiogenesis patterns into a prognostic model offers a multifaceted approach that not only predicts patient outcomes but also potentially identifies responses to immunotherapy and drug sensitivity.

The focus on angiogenesis is particularly intriguing given its pivotal role in tumor progression. It's impressive that the ANGscore was validated across various datasets, including bulk RNA-seq and single-cell RNA-seq data, as well as in immunotherapy-related datasets. Its ability to stratify patients based on prognosis and immune microenvironment characteristics signifies a substantial advancement in OS management.

The association between ANGscore and immune cell infiltration, along with its link to immune response markers like IFN-γ signaling, provides deeper insights into the tumor's behavior and potential avenues for therapeutic intervention. Furthermore, the indication that high ANGscore OS patients might exhibit resistance to certain drugs like uprosertib but sensitivity to others such as VE821, AZD6738, and BMS.345541 holds immense clinical significance.

This comprehensive approach not only offers prognostic insights but also hints at the potential for personalized treatment strategies based on individual ANGscore profiles. It's fascinating how a molecular signature related to angiogenesis can have such broad implications across prognosis, immune characteristics, and treatment responses in OS patients.

The ANGscore's potential to guide patient stratification during immunotherapy and tailor treatment plans aligns with the growing trend towards precision medicine. This research could significantly impact clinical decision-making in OS, potentially improving patient outcomes and quality of life.