Abstract
The tumor microenvironment (TME) has important effects on the tumorigenesis and development of osteosarcoma (OS). However, the dynamic mechanism regulating TME immune and matrix components remains unclear. In this study, we collected quantitative data on the gene expression of 88 OS samples from The Cancer Genome Atlas (TCGA) database and downloaded relevant clinical cases of OS from the TARGET database. The proportions of tumor-infiltrating immune cells (TICs) and the numbers of immune and matrix components were determined by CIBERSORT and ESTIMATE calculation methods. Protein-protein interaction (PPI) network construction and Cox regression analysis were conducted to analyze differentially expressed genes (DEGs). The complement components C1qA, C1qB and C1qC were then determined to be predictive factors through univariate Cox analysis and PPI cross analysis. Further analysis found that the levels of C1qA, C1qB and C1qC expression were positively linked to OS patient survival time and negatively correlated with the clinicopathological feature percent necrosis at definitive surgery. The results of gene set enrichment analysis (GSEA) demonstrated that genes related to immune functions were significantly enriched in the high C1qA, C1qB and C1qC expression groups. Proportion analysis of TICs by CIBERSORT showed that the levels of C1qA, C1qB and C1qC expression were positively related to M1 and M2 macrophages and CD8+ cells and negatively correlated with M0 macrophages. These results further support the influence of the levels of C1qA, C1qB and C1qC expression on the immune activity of the TME. Therefore, C1qA, C1qB and C1qC may be potential indicators of remodeling in the OS TME, which is helpful to predict the prognosis of patients with OS and provide new ideas for immunotherapy for OS.
Highlights
Osteosarcoma (OS), which accounts for 9% of cancer deaths in children and adolescents aged 10-24 years, is the most common primary malignant bone tumor in children and adolescents
A protein-protein interaction (PPI) network was constructed using differentially expressed genes (DEGs) identified by both ImmuneScore and StromalScore, and univariate Cox regression analysis was carried out
We continued to screen the relationships between gene expression and survival and identified C1qA, C1qB and C1qC as the focus of a follow-up series of analyses, including gene set enrichment analysis (GSEA) and correlation analysis of clinicopathological features and tumor-infiltrating immune cells (TICs)
Summary
Osteosarcoma (OS), which accounts for 9% of cancer deaths in children and adolescents aged 10-24 years, is the most common primary malignant bone tumor in children and adolescents. It has strong local invasiveness and early metastasis, with signs of metastasis indicating a poor prognosis in advanced osteosarcoma patients [1, 2]. The disease-free survival rate of OS patients is close to 70% [3]. The five-year overall survival rate is approximately 20%, which is still insufficient to a large extent [4, 5]. Identifying new diagnostic biomarkers and developing more effective molecular targets for cancer treatment are still warranted
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