Potential role of m6A RNA methylation regulators in osteosarcoma and its clinical prognostic value

J Orthop Surg Res. 2021 May 5;16(1):294. doi: 10.1186/s13018-021-02422-5.

Abstract

Background: Osteosarcoma is a disease with high mortality in children and adolescents, and metastasis is one of the important clinical features of osteosarcoma. N6-Methyladenosine (m6A) is the most abundant methylation modification in mRNA, which is regulated by m6A regulators. It is reported that it is related to the occurrence and development of tumors. However, the mechanism of its action in osteosarcoma is rarely known. The purpose of this study was to identify the potential role of m6A regulatory factor in osteosarcoma and its clinical prognostic value.

Methods: Here, we used The Cancer Genome Atlas (TCGA) to comprehensively analyze the relationship between m6A regulatory factors and osteosarcoma (metastasis group and non-metastasis group). We analyzed their survival relationship and analyzed all the m6A regulatory factors in TCGA tumor data set by using the univariate Cox proportional hazard regression model. Finally, we selected two survival-related methylation regulators (FTO and IGF2BP2) as risk gene signature.

Results: According to the median risk, patients were divided into low-risk group and high-risk group. Multivariate Cox regression analysis showed that these two risk genes were considered to be the key factors independently predicting the prognosis of patients with osteosarcoma. In addition, we verified their characteristics with gene expression omnibus (GEO) DataSets and confirmed that they are related to tumor and immune-related signaling pathways through gene set enrichment analysis (GESA) and immune infiltration analysis.

Conclusions: In conclusion, m6A regulators might play an important role in the metastasis of osteosarcoma and have potential important value for the prognosis and treatment strategy of osteosarcoma patients.

Keywords: Osteosarcoma; Prognosis; TCGA; m6A; m6A regulators.

MeSH terms

  • Adolescent
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / physiology*
  • Bone Neoplasms / genetics*
  • Bone Neoplasms / immunology
  • Bone Neoplasms / metabolism*
  • Bone Neoplasms / pathology
  • Child
  • Female
  • Forecasting
  • Gene Expression
  • Genetic Association Studies
  • Humans
  • Male
  • Methylation
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism*
  • Neoplasm Metastasis / genetics*
  • Osteosarcoma / genetics*
  • Osteosarcoma / immunology
  • Osteosarcoma / metabolism*
  • Osteosarcoma / pathology
  • Prognosis
  • RNA / metabolism*
  • RNA-Binding Proteins / physiology*
  • Regression Analysis
  • Risk
  • Signal Transduction / genetics
  • Signal Transduction / immunology

Substances

  • IGF2BP2 protein, human
  • RNA-Binding Proteins
  • RNA
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human
  • Methyltransferases
  • METTL3 protein, human