A 1p/19q Codeletion-Associated Immune Signature for Predicting Lower Grade Glioma Prognosis
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ORIGINAL RESEARCH
A 1p/19q Codeletion‑Associated Immune Signature for Predicting Lower Grade Glioma Prognosis Jie Xu1 · Fang Liu2 · Yuntao Li1 · Liang Shen2 Received: 28 June 2020 / Accepted: 30 August 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
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. Keywords Lower grade gliomas · The cancer genome atlas · Chinese glioma genome atlas · Immune · Prognosis
Introduction Glioma, which derives from glial cells, is the commonest primary intracranial malignancy and is associated with poor outcomes. Gliomas are classified into grade I, II, III, or IV (Louis et al. 2007). 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 Jie Xu and Fang Liu should be considered joint first authors. * Liang Shen [email protected] 1
Department of Neurosurgery, Huzhou Cent Hospital, Affiliated Cent Hospital Huzhou University, 198 Hongqi Road, Huzhou 313000, Zhejiang, China
Department of Neurosurgery, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, 68 Gehu Road, Changzhou 213000, Jiangsu, China
2
gliomas (LGG) (Kiran et al. 2019). The median GBM survival is 1 to 2 years after diagnosis while the overall survival (OS) for LGG patients ranges between 5 and
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