Development of an immune-related prognostic index associated with osteosarcoma

ABSTRACT

Tumor immunity is closely associated with the prognosis of tumors, including osteosarcoma (OS). The aim of the present study was to construct an immune-related prognostic index (PI) to predict the prognosis of OS. Herein, OS expression data were sourced from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database. We divided the OS patients into nonmetastatic and metastatic groups, allowing differentially immune-related genes (DIRGs) to be selected. After DIRGs were further investigated by enrichment analysis, four keys prognostic IRGs (CD79A, CSF3R, MTNR1B and NPPC) were identified using a Cox proportional hazards model. Then, an immune-related prognostic index was constructed. Finally, gene set enrichment analysis (GSEA) was employed to further explore the underlying mechanisms. The difference in tumor-infiltrating immune cell (TIIC) abundance was also discussed. In our study, eight upregulated genes and 30 downregulated genes were identified. Several Gene Ontology (GO) terms and the most significantly enriched KEGG pathways were immune-associated functions and pathways. Four genes, including CD79A, CSF3R, MTNR1B and NPPC, were used to establish a risk assessment model for evaluating OS prognosis. GSEA revealed that the risk score was related to cytokine receptor interaction and to the chemokine and B cell receptor signaling pathways. Furthermore, high risk markedly related to the infiltration of several immune cell types, including M2 macrophages, naïve CD4 T cells, and CD8 T cells. In sum, we developed a survival model for OS. The underlying molecular mechanisms of the high-risk group may affect immune-related biological processes and TIICs.Abbreviations TARGET: Therapeutically Applicable Research To Generate Effective Treatments; PI: Prognostic index; OS: Osteosarcoma; DIRGs: Differentially immune-related genes; GSEA: Gene set enrichment analysis; TIIC: Tumor-infiltrating immune cell.

Graphical abstract

KEYWORDS:

• Osteosarcoma
• tumor immunity
• prognostic index

Highlights

1. An immune-related prognostic index to predict the prognosis of OS was constructed.

2. The prognostic index is an independent index for OS prognosis.

3. The prognostic index may affect immune-related biological processes and TIICs.

Authors’ contributions

CDY conceived the study and performed the bioinformatics analyses. YLH and XRL downloaded and organized the clinical and gene expression data. CDY and YSH performed the statistical analyses. CDY and JL wrote the manuscript. YSH, XPW, CJL and XHT critically revised the article for essential intellectual content and administrative support. All authors read and approved the final manuscript.

Availability of data and materials

All analyzed data are included in this published article and its supplementary information file. The original data are available upon reasonable request to the corresponding author.

Disclosure statement

Authors Chao-Dong Ying, Ying-Lan Hou, Xiao-Ren Liu, Yu-Sheng He, Xing-Ping Wang, Cheng-Jie Li, Xiao-Hong Tan, Jun Liu declare that they have no conflicts of interest.

Ethics approval and consent to participate

Not applicable. All data in this study are publicly available.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was not funded by any grant.