Abstract
Lower grade gliomas (LGGs) with codeletion of chromosomal arms 1p and 19q (1p/19 codeletion) have a favorable outcome. However, its overall survival (OS) varies. Here, we established an immune signature associated with 1p/19q codeletion for accurate prediction of prognosis of LGGs. The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases with RNA sequencing and corresponding clinical data were dichotomized into training group and testing group. The immune-related differentially expressed genes (DEGs) associated with 1p/19q codeletion were screened using Cox proportional hazards regression analyses. A prognostic signature was established using dataset from CGGA and tested in TCGA database. Subsequently, we explored the correlation between the prognostic signature and immune response. Thirteen immune genes associated with 1p/19q codeletion were used to construct a prognostic signature. The 1-, 3-, 5-year survival rates of the low-risk group were approximately 97%, 89%, and 79%, while those of the high-risk group were 81%, 50% and 34%, respectively, in the training group. The nomogram which comprised age, WHO grade, primary or recurrent types, 1p/19q codeletion status and risk score provided accurate prediction for the survival rate of glioma. DEGs that were highly expressed in the high-risk group clustered with many immune-related pathways. Immune checkpoints including TIM3, PD1, PDL1, CTLA4, TIGIT, MIR155HG, and CD48 were correlated with the risk score. VAV3 and TNFRFSF11B were found to be candidate immune checkpoints associated with prognosis. The 1p/19q codeletion-associated immune signature provides accurate prediction of OS. VAV3 and TNFRFSF11B are novel immune checkpoints.
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Data Availability
The RNA-seq data and corresponding clinical information were observed from the TCGA (https://portal.gdc.cancer.gov/) and CGGA (https://www.cgga.org.cn). The immune-related gene list was got from the IMMPORT website (https://www.immport.org/).
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Acknowledgements
We would like to acknowledge the researchers’ contribution to the TCGA, CGGA databases and support of the fund of Jiangsu Provincial Key Research and Development Program (No. BE2019652) and the Youth Program of Changzhou No.2 People’s Hospital (No. 2020K001).
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This work was supported by the Jiangsu Provincial Key Research and Development Program (No. BE2019652) and the Youth Program of Changzhou No. 2 People’s Hospital (No. 2020K001).
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by JX, FL and LS; The first draft of the manuscript was written by JX and FL and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Xu, J., Liu, F., Li, Y. et al. A 1p/19q Codeletion-Associated Immune Signature for Predicting Lower Grade Glioma Prognosis. Cell Mol Neurobiol 42, 709–722 (2022). https://doi.org/10.1007/s10571-020-00959-3
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DOI: https://doi.org/10.1007/s10571-020-00959-3