Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma

Xiangyang Deng; Dongdong Lin; Bo Chen; Xiaojia Zhang; Xingxing Xu; Zelin Yang; Xuchao Shen; Liang Yang; Xiangqi Lu; Hansong Sheng; Bo Yin; Nu Zhang; Jian Lin

doi:10.3389/fonc.2019.01310

Development and Validation of an IDH1-Associated Immune Prognostic Signature for Diffuse Lower-Grade Glioma

Front Oncol. 2019 Nov 22:9:1310. doi: 10.3389/fonc.2019.01310. eCollection 2019.

Authors

Xiangyang Deng¹, Dongdong Lin¹, Bo Chen², Xiaojia Zhang¹, Xingxing Xu³, Zelin Yang¹, Xuchao Shen¹, Liang Yang¹, Xiangqi Lu¹, Hansong Sheng¹, Bo Yin¹, Nu Zhang¹, Jian Lin¹

Affiliations

¹ Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
² The Second Clinical Medical College, Wenzhou Medical University, Wenzhou, China.
³ School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou, China.

Abstract

A mutation in the isocitrate dehydrogenase 1 (IDH1) gene is the most common mutation in diffuse lower-grade gliomas (LGGs), and it is significantly related to the prognosis of LGGs. We aimed to explore the influence of the IDH1 mutation on the immune microenvironment and develop an IDH1-associated immune prognostic signature (IPS) for predicting prognosis in LGGs. IDH1 mutation status and RNA expression were investigated in two different public cohorts. To develop an IPS, LASSO Cox analysis was conducted for immune-related genes that were differentially expressed between IDH1^wt and IDH1^mut LGG patients. Then, we systematically analyzed the influence of the IPS on the immune microenvironment. A total of 41 immune prognostic genes were identified based on the IDH1 mutation status. A four-gene IPS was established and LGG patients were effectively stratified into low- and high-risk groups in both the training and validation sets. Stratification analysis and multivariate Cox analysis revealed that the IPS was an independent prognostic factor. We also found that high-risk LGG patients had higher levels of infiltrating B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages and dendritic cells, and expressed higher levels of CTLA-4, PD-1 and TIM-3. Moreover, a novel nomogram model was established to estimate the overall survival in LGG patients. The current study provides novel insights into the LGG immune microenvironment and potential immunotherapies. The proposed IPS is a clinically promising biomarker that can be used to classify LGG patients into subgroups with distinct outcomes and immunophenotypes, with the potential to facilitate individualized management and improve prognosis.

Keywords: IDH1; immune prognostic signature; lower-grade glioma; mutation; nomogram.