Immune-related prognosis biomarkers associated with osteosarcoma microenvironment

Weifeng Hong,Zifang Huang,Junlin Yang,Yujun Gu,Liheng Ma,Mouyuan Liu,Yayun Ji,Hong Yuan

doi:10.1186/s12935-020-1165-7

Abstract

BackgroundOsteosarcoma is a highly aggressive bone tumor that most commonly affects children and adolescents. Treatment and outcomes for osteosarcoma have remained unchanged over the past 30 years. The relationship between osteosarcoma and the immune microenvironment may represent a key to its undoing.MethodsWe calculated the immune and stromal scores of osteosarcoma cases from the Target database using the ESTIMATE algorithm. Then we used the CIBERSORT algorithm to explore the tumor microenvironment and analyze immune infiltration of osteosarcoma. Differentially expressed genes (DEGs) were identified based on immune scores and stromal scores. Search Tool for the Retrieval of Interacting Genes Database (STRING) was utilized to assess protein–protein interaction (PPI) information, and Molecular Complex Detection (MCODE) plugin was used to screen hub modules of PPI network in Cytoscape. The prognostic value of the gene signature was validated in an independent GSE39058 cohort. Gene set enrichment analysis (GSEA) was performed to study the hub genes in signaling pathways.ResultsFrom 83 samples of osteosarcoma obtained from the Target dataset, 137 DEGs were identified, including 134 upregulated genes and three downregulated genes. Functional enrichment analysis and PPI networks demonstrated that these genes were mainly involved in neutrophil degranulation and neutrophil activation involved in immune response, and participated in neuroactive ligand–receptor interaction and staphylococcus aureus infection.ConclusionsOur study established an immune-related gene signature to predict outcomes of osteosarcoma, which may be important targets for individual treatment.

Highlights

Osteosarcoma is a highly aggressive bone tumor that most commonly affects children and adolescents
Immune scores and stromal scores are associated with osteosarcoma clinical status We downloaded gene expression profiles and clinical information of all 83 osteosarcoma patients with initial pathologic diagnosis from the Target database
To explore the potential correlation between immune/ stromal scores and clinical information, we divided osteosarcoma patients according to tumor location, age, gender, metastasis status and race

Summary

Introduction

Osteosarcoma is a highly aggressive bone tumor that most commonly affects children and adolescents. Treatment and outcomes for osteosarcoma have remained unchanged over the past 30 years. Osteosarcoma is the primary malignant bone cancer that most commonly affects children, adolescents, and young adults [1]. Osteosarcoma exhibits a predilection to occur in the metaphysis of long bones, and most commonly occurs in the distal femur (43%), proximal tibia (23%), or humerus (10%) [3]. Clinical outcomes and treatment modalities for osteosarcoma have not changed for more than 30 years. Hong et al Cancer Cell Int (2020) 20:83 intensified postoperative chemotherapy for high-grade patients failed to improve survival [4, 5], underscoring a critical need for new treatment strategies. The high morbidity and mortality burden in osteosarcoma necessitates additional research to characterize and understand the underlying mechanisms [6, 7]

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Discussion

Conclusion