Abstract
Background IDH mutation is the most common in diffuse LGGs, correlated with a favorable prognosis. However, the IDH-mutant LGGs patients with poor prognoses need to be identified, and the potential mechanism leading to a worse outcome and treatment options needs to be investigated. Methods A six-gene immune-related prognostic signature in IDH-mutant LGGs was constructed based on two public datasets and univariate, multivariate, and LASSO Cox regression analysis. Patients were divided into low- and high-risk groups based on the median risk score in the training and validation sets. We analyzed enriched pathways and immune cell infiltration, applying the GSEA and the immune evaluation algorithms. Results Stratification and multivariate Cox analysis unveiled that the six-gene signature was an independent prognostic factor. The signature (0.806/0.795/0.822) showed a remarkable prognostic performance, with 1-, 3-, and 5-year time-dependent AUC, higher than for grade (0.612/0.638/0.649) and 1p19q codeletion status (0.606/0.658/0.676). High-risk patients had higher infiltrating immune cells. However, the specific immune escape was observed in the high-risk group after immune activation, owing to increasing immunosuppressive cells, inhibitory cytokines, and immune checkpoint molecules. Moreover, a novel nomogram model was developed to evaluate the survival in IDH-mutant LGGs patients. Conclusion The six-gene signature could be a promising prognostic biomarker, which is promising to promote individual therapy and improve the clinical outcomes of IDH-mutant gliomas. The study also refined the current classification system of IDH-mutant gliomas, classifying patients into two subtypes with distinct immunophenotypes and overall survival.
Highlights
Gliomas are the most common intracranial primary tumor, including nondiffuse gliomas and diffuse gliomas [1]
Survival analysis was carried based on the Kaplan–Meier method and the log-rank test to evaluate the prognostic performance of the six-gene signature. e area under the curve (AUC) was calculated from the time-dependent receiver operating characteristic (ROC) curves to assess the sensitivity and specificity by using the “survivalROC” R package
We screened 7598 and 3518 genes that were significantly correlated with overall survival from the IDH-mutant LGGs cohort of CGGA_693 (n 288) and TCGA (n 385) by applying univariate Cox regression analysis, respectively (Figure 1(a)). en, we divided these genes into risky genes (HR > 1) and protective genes (HR < 1) based on hazard ratios (HR) values in the CGGA_693 and TCGA cohorts
Summary
Gliomas are the most common intracranial primary tumor, including nondiffuse gliomas and diffuse gliomas [1]. Gliomas patients harboring IDH mutations, including IDH1 and IDH2 mutation, have a better prognosis than the wild type [3]. Most of the LGGs with IDH wild type were molecularly and clinically analogous to primary glioblastoma [4]. IDH mutations often occur in LGGs patients with incidences of up to 75%, while the mutation frequency of IDH1 is lower in glioblastoma (12%) [5, 6]. A six-gene immune-related prognostic signature in IDH-mutant LGGs was constructed based on two public datasets and univariate, multivariate, and LASSO Cox regression analysis. High-risk patients had higher infiltrating immune cells. A novel nomogram model was developed to evaluate the survival in IDH-mutant LGGs patients. E six-gene signature could be a promising prognostic biomarker, which is promising to promote individual therapy and improve the clinical outcomes of IDH-mutant gliomas. Conclusion. e six-gene signature could be a promising prognostic biomarker, which is promising to promote individual therapy and improve the clinical outcomes of IDH-mutant gliomas. e study refined the current classification system of IDH-mutant gliomas, classifying patients into two subtypes with distinct immunophenotypes and overall survival
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