ABCD3 is a prognostic biomarker for glioma and associated with immune infiltration: A study based on oncolysis of gliomas

Front Cell Infect Microbiol. 2022 Jul 25;12:956801. doi: 10.3389/fcimb.2022.956801. eCollection 2022.

Abstract

Background: Gliomas are the most lethal primary brain tumors and are still a major therapeutic challenge. Oncolytic virus therapy is a novel and effective means for glioma. However, little is known about gene expression changes during this process and their biological functions on glioma clinical characteristics and immunity.

Methods: The RNA-seq data after oncolytic virus EV-A71 infection on glioma cells were analyzed to screen significantly downregulated genes. Once ABCD3 was selected, The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Genotype-Tissue Expression (GTEx), Clinical Proteomic Tumor Analysis Consortium (CPTAC), and Human Protein Atlas (HPA) data were used to analyze the relationship between ABCD3 expression and clinical characteristics in glioma. We also evaluated the influence of ABCD3 on the survival of glioma patients. CIBERSORT and Tumor Immune Estimation Resource (TIMER) were also used to investigate the correlation between ABCD3 and cancer immune infiltrates. Gene set enrichment analysis (GSEA) was performed to functionally annotate the potential functions or signaling pathways related to ABCD3 expression.

Results: ABCD3 was among the top 5 downregulated genes in glioma cells after oncolytic virus EV-A71 infection and was significantly enriched in several GO categories. Both the mRNA and protein expression levels of ABCD3 were upregulated in glioma samples and associated with the prognosis and grades of glioma patients. The Kaplan-Meier (K-M) curve analysis revealed that patients with high ABCD3 expression had shorter disease-specific survival (DSS) and overall survival (OS) than those with low ABCD3 expression. Moreover, ABCD3 expression could affect the immune infiltration levels and diverse immune marker sets in glioma. A positive correlation was found between ABCD3 and macrophages and active dendritic cells in the microenvironment of both the GBM and LGG. Gene sets including the plk1 pathway, tyrobp causal network, ir-damage and cellular response, and interleukin-10 signaling showed significant differential enrichment in the high ABCD3 expression phenotype.

Conclusion: Our results suggested that ABCD3 could be a potential biomarker for glioma prognosis and immunotherapy response and also further enriched the theoretical and molecular mechanisms of oncolytic virus treatment for malignant gliomas.

Keywords: ABCD3; biomarker; glioma; immune infiltrates; oncolytic virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / therapy
  • Glioma* / genetics
  • Glioma* / therapy
  • Humans
  • Prognosis
  • Proteomics
  • Tumor Microenvironment / genetics

Substances

  • Biomarkers, Tumor