Affiliation:
1. The Third Xiangya Hospital of Central South University
Abstract
Abstract
Although neoadjuvant chemotherapy combined with surgical resection improved the prognosis of patients with osteosarcoma, there was no significant effect on metastatic and recurrent osteosarcoma. Immunotherapy seems to have turned the corner. However, as an important target of immunotherapy, the relationship between the phenotype of Tumor-associated macrophages and the prognosis of osteosarcoma remains unclear. In single-cell RNA sequencing, the relationship between macrophages and immunotherapy in the osteosarcoma microenvironment was analyzed, and the hub genes closely related to macrophage polarization were revealed. The least absolute shrinkage and selection operator algorithm and multivariate Cox regression analysis were performed to constructed long-term survival predictive strategies which was further validated in the GEO cohort. Multiple machine learning algorithms were then used to screen for target gene, which was then used for pan-cancer analysis. Finally, immunotherapy predictions were made using TIDE and TCIA databases. We found that macrophages are closely related to immune checkpoint inhibitors and identified 141 genes regulating macrophage polarization, from which 8 genes were selected to construct prognostic models. Significant variations between high-risk and low-risk groups were found in the activation of immune cells, immune-related signaling pathways and immune function. Lastly, the prognostic model and the identified target-gene (BNIP3) may provide more precise immunotherapy options for osteosarcoma and other tumors. In general, the constructed prognostic model of genes that regulating macrophage polarization can provide precise immunotherapy regimen and the quintessential insights into follow-up mechanisms in existing studies. Furthermore, BNIP3 may be a potential immunotherapeutic intervention target for tumors including osteosarcoma.
Publisher
Research Square Platform LLC