Prognostic and predictive value of an immune infiltration signature in diffuse lower-grade gliomas

Abstract

BACKGROUND. Lower-grade gliomas (LGGs) vary widely in terms of the patient's overall survival (OS). There is no current, valid method that could exactly predict the survival. The effects of intratumoral immune infiltration on clinical outcome have been widely reported. Thus, we aim to develop an immune infiltration signature to predict the survival of LGG patients. METHODS. We analyzed 1216 LGGs from 5 public data sets, including 2 RNA sequencing data sets and 3 microarray data sets. Least absolute shrinkage and selection operator (LASSO) Cox regression was used to select an immune infiltration signature and build a risk score. The performance of the risk score was assessed in the training set (329 patients), internal validation set (140 patients), and 4 external validation sets (405, 118, 88, and 136 patients). RESULTS. An immune infiltration signature consisting of 20 immune metagenes was used to generate a risk score. The performance of the risk score was thoroughly verified in the training and validation sets. Additionally, we found that the risk score was positively correlated with the expression levels of TGF-β and PD-L1, which were important targets of combination immunotherapy. Furthermore, a nomogram incorporating the risk score, patient's age, and tumor grade was developed to predict the OS, and it performed well in all the training and validation sets (C-index: 0.873, 0.881, 0.781, 0.765, 0.721, and 0.753). CONCLUSION. The risk score based on the immune infiltration signature has reliable prognostic and predictive value for patients with LGGs and is a potential biomarker for the cotargeting immunotherapy.

The Diagnostic Value of Preoperative Hematology Makers in the Classification and Molecular Subtypes of Newly Diagnosed High-Grade Gliomas

“…Furthermore, we further analyzed the relationship between hematological indicators and IDH mutation subgroups, and found that only FIB had a signi cant difference between G4 IDH-wt and G3 IDH-mut or G4 IDH-mut. Previous study had shown that the immune response of the tumor microenvironment was more susceptible to the modulation of IDH mutation status in lower-grade gliomas 15 . This result suggested that there may be a connection between systemic and local in ammation and coagulation and immune regulation.…”

Prognostic and Predictive Value of Immune-Related Gene Pair Signature in Primary Lower-Grade Glioma Patients

“…To date, some existing models have used IRGs as a prognostic predictor of glioma patients (33,34). A study examining the gene expression pattern of tumor immune infiltration identified an association with LGG malignancy, and a risk model based on 20 IRGs with different expression levels was shown to present decent OS prediction abilities for LGG (13). However, many prognosis-related models are limited by factors such as small sample size and the lack of sufficient validation.…”

“…IRGs have also been regarded as biomarkers to predict prognosis of cancer patients (12). A recent study constructed a stable IRG signature that was found to serve as an effective and predictive prognostic model among primary LGG patients (13).…”

A Prognostic Nomogram and Risk Stratification in Pediatric With Hemisphere Lower-Grade Gliomas: a SEER-Based Study 1998-2016

“…Tumor grade was a good predictor of survival, and both previous and the present found the association between WHO grade II gliomas and better OS . Different immune in ltration types may contribute to the difference in prognosis between Oligodendroglioma and astrocytoma (Song and Weng et al, 2020). Pleomorphic xanthoastrocytoma (PXA) is a rare brain tumor mainly affecting pediatric and young adults (Vaubel and Zschernack et al, 2020).…”