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.
Highlights
Glioma is the most common and deadly primary malignant tumor in the central nervous system [1]
Because few investigators have studied the relationship between integrated stress response (ISR) and the malignant progression of low-grade glioma (LGG), we systematically analyzed the clinical value of the ISR in LGGs
We found that endoplasmic reticulum stress, nutritional deprivation, and redox imbalance in the ISR correlated with age, isocitrate dehydrogenase 1 (IDH1), 1p19q, and other significant LGG survival prognostic markers
Summary
Glioma is the most common and deadly primary malignant tumor in the central nervous system [1]. Gliomas can be divided into high-grade glioma and low-grade glioma (LGG). Increasing studies have reported that many LGG patients have a tendency toward malignant transformation, which can transform into higher grades, leading to adverse outcomes [6]. 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. 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 established an accurate integrated stress response risk signature for predicting cluster 2. 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
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