Abstract
Gliomas with chromosome 1p/19q codeletion were considered a specific tumor entity. This study was designed to reveal the biological function alterations tightly associated with 1p/19q codeletion in gliomas. Clinicopathological and RNA sequencing data from glioma patients were obtained from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Gene set variation analysis was performed to explore the differences in biological functions between glioma subgroups stratified by 1p/19q codeletion status. The abundance of immune cells in each sample was detected using the CIBERSORT analytical tool. Single-cell sequencing data from public databases were analyzed using the t-distributed stochastic neighbor embedding (t-SNE) algorithm, and the findings were verified by in vitro and in vivo experiments and patient samples.We found that the activation of immune and inflammatory responses was tightly associated with 1p/19q codeletion in gliomas. As the most important transcriptional regulator of Galectin-9 in gliomas, the expression level of CCAAT enhancer-binding protein alpha in samples with 1p/19q codeletion was significantly decreased, which led to the downregulation of the immune checkpoints Galectin-9 and TIM-3. These results were validated in three independent datasets. The t-SNE analysis showed that the loss of chromosome 19q was the main reason for the promotion of the antitumor immune response. IHC protein staining, in vitro and in vivo experiments verified the results of bioinformatics analysis. In gliomas, 1p/19q codeletion can promote the antitumor immune response by downregulating the expression levels of the immune checkpoint TIM-3 and its ligand Galectin-9.
Highlights
Gliomas, the most common and lethal primary intracranial tumor in adults, are characterized by strong invasiveness and a high recurrence rate [1,2,3]
We found that the immune system process was most tightly correlated with the 1p/19q codeletion status in the glioma samples (Figures 1D–F)
These results indicated that 1p/19q codeletion may play an essential role in the regulation of the tumor immune microenvironment of gliomas
Summary
The most common and lethal primary intracranial tumor in adults, are characterized by strong invasiveness and a high recurrence rate [1,2,3]. Tumor-specific molecular alterations, such as isocitrate dehydrogenase 1 (IDH1) mutation and the codeletion of chromosome arms 1p and 19q (1p/19q codeletion), could serve as prognostic indicators or therapeutic targets for glioma patients [4,5,6]. These biomarkers were included in the 2016 World Health Organization (WHO) Classification of Tumors of the Central Nervous System (CNS), providing an important theoretical foundation for the diagnosis and individualized treatment of gliomas [7]. We hypothesized that 1p/19q codeletion may improve glioma sensitivity to postoperative treatment by regulating the tumor immune microenvironment
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