A five-microRNA signature for individualized prognosis evaluation and radiotherapy guidance in patients with diffuse lower-grade glioma

Abstract

Despite the prognostic value of IDH and other gene mutations found in diffuse glioma, markers that judge individual prognosis of patients with diffuse lower-grade glioma (LGG) are still lacking. This study aims to develop an expression-based microRNA signature to provide survival and radiotherapeutic response prediction for LGG patients. MicroRNA expression profiles and relevant clinical information of LGG patients were downloaded from The Cancer Genome Atlas (TCGA; the training group) and the Chinese Glioma Genome Atlas (CGGA; the test group). Cox regression analysis, random survival forests-variable hunting (RSFVH) screening and receiver operating characteristic (ROC) were used to identify the prognostic microRNA signature. ROC and TimeROC curves were plotted to compare the predictive ability of IDH mutation and the signature. Stratification analysis was conducted in patients with radiotherapy information. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore the biological function of the signature. We identified a five-microRNA signature that can classify patients into low-risk or high-risk group with significantly different survival in the training and test datasets (P < 0.001). The five-microRNA signature was proved to be superior to IDH mutation in survival prediction (AUCtraining = 0.688 vs 0.607). Stratification analysis found the signature could further divide patients after radiotherapy into two risk groups. GO and KEGG analyses revealed that microRNAs from the prognostic signature were mainly enriched in cancer-associated pathways. The newly discovered five-microRNA signature could predict survival and radiotherapeutic response of LGG patients based on individual microRNA expression.

Keywords: diffuse lower-grade glioma; microRNA; prognostic; radiotherapeutic response; signature.