Identification of Immune-Related Genes MSR1 and TLR7 in Relation to Macrophage and Type-2 T-Helper Cells in Osteosarcoma Tumor Micro-Environments as Anti-metastasis Signatures

Metastasis of osteosarcoma (OS) is an essential factor affecting the prognosis and survival of patients. The tumor microenvironment, including tumor immune-infiltrating cells (TIIC), is closely related to tumor progression. The purpose of this study was to investigate the differences between metastatic and non-metastatic immune-infiltrating cells in OS and to identify key immune-related genes. The differences in immune infiltration in OS metastasis were calculated based on the ssGSEA algorithm of 28 immuno-infiltrating cells. Weighted gene co-expression network analysis (WGCNA) and intersection analysis were used to screen immune-related modules and hubgenes. Univariate/multivariate/Lasso Cox regressions were used for models construction and signatures screening. The receiver operating characteristic (ROC) and Kaplan-Meier (K-M) curves were constructed to observe the metastases of different groups. Both internal and external data were verified. We found that macrophages and Type-2 T-helper cells were significantly decreased in patients with OS metastases. The high-risk groups obtained from multivariate/Lasso Cox models constructed with 11 immune-related hubgenes almost all underwent distant metastases within 5 years. Interestingly and importantly, two genes, MSR1 and TLR7, appeared in various models and various hubgenes, which play an anti-metastasis role and may prolong overall survival in OS. Our study may help elucidate the impact of TIIC on OS metastasis outcomes and to identify biomarkers and therapeutic targets.