The N6-Methylandenosine-Related Gene BIRC5 as a Prognostic Biomarker Correlated With Cell Migration and Immune Cell Infiltrates in Low Grade Glioma.

Abstract

Gliomas account for 75% of all primary malignant brain tumors in adults and are associated with high mortality. Emerging evidence has demonstrated that baculoviral inhibitor of apoptosis repeat containing 5 (BIRC5) plays a critical role in cell apoptosis and the progression of diverse cancers. However, no studies have yet focused on the immunological function and mechanisms of upstream BIRC5 regulation in the progression of low-grade gliomas (LGG). Here, we evaluated BIRC5 expression and clinical characteristics in people with LGG using the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, Gene Expression Omnibus, Rembrandt, and Gravendeel databases. We used Kaplan–Meier statistics and receiver operating characteristic (ROC) curves to analyze the prognostic value of BIRC5 in LGG. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment terms were also explored to identify functional roles of BIRC5. The Tumor Immune Estimation Resource (TIMER) and Tumor Immune System Interaction (TISIDB) databases were used to examine the correlation between BIRC5 expression and immune cell infiltration in LGG. The Genomics of Drug Sensitivity in Cancer (GDSC) and Cancer Therapeutics Response Portal (CTRP) databases were used to examine the potential drugs targeting BIRC5. We used transwell and wound healing assays to determine the biological functions of BIRC5 in glioma cell migration. Our results demonstrated that BIRC5 was highly expressed in LGG and the expression level correlated with tumor grade, prognosis, histological subtype, isocitrate dehydrogenase 1 (IDH1) mutation, 1p/19q chromosomal co-deletion, chemotherapy status, and O[6]-methylguanine-DNA methyltransferase (MGMT) promoter methylation status. GO and KEGG analysis showed that BIRC5 is primarily involved in cell proliferation and immune response-related signaling pathways. We also found that BIRC5 was significantly correlated with m6A modification and diverse drug sensitivity. TIMER and TISIDB database analysis showed that BIRC5 expression is associated with infiltration of diverse immune cells and immune modulation in LGG. BIRC5 knockdown inhibited LGG cell migration. Collectively, our results demonstrate that BIRC5 is correlated with cell migration and immune infiltration in LGG and may be a useful prognostic biomarker.