Multiomics Profiling and Clustering of Low-Grade Gliomas Based on the Integrated Stress Status

Abstract

Background. Although the prognosis of low-grade glioma is better than that of glioblastoma, there are still some groups with poor prognosis. The integrated stress response contributes to the malignant progress of tumors. As there had limited research focused on the integrated stress status in LGG, it is urgent to profile and reclassify LGG based on the integrated stress response. Methods. Information of glioma patients was obtained from the Chinese Glioma Genome Atlas, The Cancer Genome Atlas, and the GSE16011 cohorts. Statistical analyses were conducted using GraphPad Prism 8 and R language. Results. We summarized and quantified four types of integrated stress responses. Relationships between these four types of stress states and the clinical characteristics were analyzed in low-grade glioma. We then reclassified the patients based on these four scores and found that cluster 2 had the worst prognosis, while cluster 1 had the best prognosis. We also established an accurate integrated stress response risk signature for predicting cluster 2. We found that immune response and suppressive immune cell components were more enriched in the high-risk group. We also profiled the genomic differences between the low- and high-risk groups, including the nonmissense mutation of driver genes and the copy number variations. Conclusion. Low-grade glioma patients were divided into three clusters based on the integrated stress status, with cluster 2 exhibiting malignant transformation trends. The signature adequately reflected the traits of cluster 2, while a high risk score indicated a worse prognosis and an enriched inhibitory immune microenvironment.