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

Zhiyu Chen; Huanhuan Huang; Yang Wang; Fangbiao Zhan; Zhengxue Quan

doi:10.3389/fmolb.2020.576298

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

Front Mol Biosci. 2020 Dec 14:7:576298. doi: 10.3389/fmolb.2020.576298. eCollection 2020.

Authors

Zhiyu Chen^{1

2}, Huanhuan Huang², Yang Wang^{1

2}, Fangbiao Zhan^{1

2}, Zhengxue Quan¹

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
² The First Clinical College, Chongqing Medical University, Chongqing, China.

Abstract

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.

Keywords: TLR7; MSR1; macrophages; metastasis; osteosarcoma; tumor immune infiltration cell; type-2 T-helper cell.