Novel interferon-gamma-related 2-gene signature predicts outcome and responsiveness to immune checkpoint blockade in glioma

Background Glioma represents the most common and aggressive brain malignancy. Interferon-gamma (IFNG)-related gene signatures have been shown of clinical significance in multiple cancers, while its role in glioma remains less addressed. Methods A total of 2933 glioma samples ranging from WHO grade II to IV with corresponding demographics were included. Multiple bioinformatics and machine learning algorithms were employed to establish an IFNG-related biomarker to classify survival differences and to elucidate the potential of glioma to respond to immune checkpoint blockade (ICB) therapy. Results The ssGSEA score of IFNGR1 and IFNGR2 was defined as the IFNGR score, which well-characterized the IFNG response in the glioma microenvironment. Increased IFNGR score was associated with clinicopathological parameters characterizing glioma malignancy, including WHO grade IV, mesenchymal subtype, and molecular biomarkers, including IDH1 wildtype, 1p19q non-codeletion, and unmethylated MGMT promoter. Consequently, K-M and Cox regression analysis found that the IFNGR score was a robust prognostic biomarker that was associated with tumor relapse for patients in certain subgroups. Moreover, the IFNGR-based group had the potential to predict ICB responsiveness, as effectively as previously validated IFNG-related gene signatures. Conclusion Together, we have developed a concise biomarker of clinical significance that may improve the current diagnosis and treatment of glioma.