AUTHOR=Li Jinchuan , Zhang Yi , Qu Zhizhao , Ding Rui , Yin Xiaofeng 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.956801

DOI=10.3389/fcimb.2022.956801

ISSN=2235-2988

ABSTRACT=Abstract
Background: Gliomas are the most lethal primary brain tumors and are still a major therapeutic challenge. Oncolytic viruses’ therapy is a novel and effective means for glioma. However, little is known about gene expression changes during this process, and their biological functions to glioma clinical characteristics and immunity.
Methods: The RNA-seq data after oncolytic virus EV-A71 infection on glioma cells was 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 survival of glioma patients. CIBERSORT and Tumor Immune Estimation Resource (TIMER) are 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 down-regulated genes in glioma cells after oncolytic viruses EV-A71 infection and significant enriched in several Go categories. Both mRNA and protein expression of ABCD3 were up-regulated in glioma samples and associated with prognosis and grades of glioma patients. Kaplan-Meier (K-M) curves 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 GBM and LGG. Gene sets including plk1 pathway, tyrobp causal network, ir-damage and cellular response and interleukin 10 signaling were showed significantly differential enrichment in ABCD3 high 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 viruses’ treatment for malignant gliomas.