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.
Highlights
Lower grade gliomas (LGGs) with codeletion of chromosomal arms 1p and 19q (1p/19 codeletion) has a favorable outcome
Thirteen immune genes associated with 1p/19q codeletion were identified and used to construct a prognostic signature
The nomogram which comprised of age, world health organization (WHO) grade, primary or recurrent types, 1p/19q codeletion status and risk score provided accurate prediction for the survival rate of glioma
Summary
Lower grade gliomas (LGGs) with codeletion of chromosomal arms 1p and 19q (1p/19 codeletion) has a favorable outcome. Gliomas are classified into grade I, II, III, or IV [1] Those in histological grade IV, such as glioblastoma (GBM), are considered high-grade gliomas, while those in grade II and III are regarded as lower grade gliomas (LGG) [2]. The median GBM survival is 1 to 2 years after diagnosis while the overall survival (OS) for LGG patients ranges between 5 and 10 years. Despite advances in cancer screening, diagnosis and treatment, LGGs often progresses into high grade glioma within years [2,3,4]. While LGG patients experience a longer survival times and a better quality of life, progression into GBM, is associated with poor therapeutic options and significantly lower prognosis. Effective LGGs treatments are of utmost importance for improved glioma outcomes
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