IL13RA2 is overexpressed in malignant gliomas and related to clinical outcome of patients.

Objective: To study the expression of IL13RA2 in gliomas and to analyze its correlation with clinicopathological/molecular features, immune cell infiltration and prognostic significance.

Methods: mRNA expression data for IL13RA2 were downloaded and analyzed from two open access datasets (TCGA & CGGA). IL13RA2 protein expression was examined by immunohistochemistry. The association between IL13RA2 and important clinicopathological/molecular markers was examined using χ and Spearman correlation tests. The TIMER tool was used to evaluate the correlation of IL13RA2 with multiple intra-tumoral immune cell types in glioma. Kaplan-Meier test and multivariate Cox analyses were applied to evaluate the prognosis.

Results: Out of the 297 glioma tissues and 20 normal brain tissues in our cohort, IL13RA2 protein was highly expressed in 115 glioma tissues (115/297, 38.7%), but no expression was detected in normal brain tissues (0/20, 0%). The expression of IL13RA2 was significantly higher in GBMs (P<0.001). More than half of GBMs (68/132, 51.5%) were high expression of IL13RA2 protein, especially GBM patients with IDH wild-type and TERT promoter mutated (60/78, 76.9%). Moreover, 11/13 (84.6%) diffuse midline gliomas and 31/51 (64.7%) IDH wild-type LGGs also highly expressed IL13RA2 in our cohorts. Chi-square test showed that the expression of IL13RA2 was correlated with patient age, WHO grade, Ki67 index, IDH status, TERT promoter status and immune cell infiltration. Additionally, IL13RA2 was strongly associated with patients' OS and served as a negative prognostic marker in infiltrating gliomas.

Conclusion: IL13RA2 was high expression in some glioma subtypes, and significantly correlated with poor prognosis. Based on its role in CAR-T therapy, it might act as an extremely important and specific therapeutic target for human malignant gliomas, especially in IDH wild-type LGG, "IDH wild-type and TERT promoter mutated" GBM and H3K27M-mutated diffuse midline glioma, and improve the clinical outcomes of these patients.