Identification of IGF2BP3 as an Adverse Prognostic Biomarker of Gliomas

Abstract

N6-methyladenosine (m⁶A) RNA modification can alter gene expression and function by regulating RNA splicing, stability, translocation, and translation. It is involved in various types of cancer. However, its role in gliomas is not well known. This study aimed to determine the prognostic value of the m⁶A RNA methylation regulator in gliomas and investigate the underlying mechanisms of the aberrant expression of m⁶A-related genes.mRNA expression profiles and clinical information of 448 glioma samples were obtained from The Cancer Genome Atlas and cBioportal. The expression of m⁶A-related genes in normal controls and low-grade glioma and glioblastoma was obtained from Gene Expression Profiling Interactive Analysis. Further, m⁶A-related gene expression and its relationship with prognosis were obtained through The Chinese Glioma Genome Atlas (CGGA). Multivariate Cox regression analyses were performed, and a nomogram was built with potential risk factors based on a multivariate Cox analysis to predict survival probability. Online tools such as Gene Set Enrichment Analysis, STRING, Cytoscape, and Molecular Complex Detection were applied for bioinformatics analysis and to investigate the underlying mechanisms of the aberrant expression of m⁶A-related genes. The multivariate Cox regression analysis found that higher expression levels of YTHDC2 and insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3, also called IMP3) were independent negative and positive prognostic factors for overall survival (OS), respectively. Data from the CGGA database showed that IGF2BP3 expression increased when the tumor grade increased. Receiver operating characteristic (ROC) curve was used to evaluate the predictive specificity and sensitivity. The area under the ROC curve indicated that the OS prediction was 0.92 (1-year) and 0.917 (3-years), indicating that m⁶A-related genes could predict patient survival. In addition, IGF2BP3 was closely related to the shorter survival period of patients. Copy number variation and DNA methylation, but not somatic mutations, might contribute to the abnormal upregulation of IGF2BP3 in gliomas. Significantly altered genes were identified, and the protein-protein interaction network was constructed. Based on the data presented, our study identified several m⁶A-related genes, especially IGF2BP3, that could be potential prognostic biomarkers of gliomas. The study unveiled the potential regulatory mechanism of IGF2BP3 in gliomas.

Keywords: IGF2BP3; M6A RNA methylation; glioma bioinformatics analysis; post-transcriptional modification; prognosis.