Integrin Alpha L as an Immune-Related Biomarker Correlated with the Prognosis and Effect of Immunotherapy in Gliomas

Abstract

Backgroud: Discovering effective immune-related biomarkers is vital to ensure efficient immunotherapy for glioma patients. Integrin Alpha L(ITGAL), essential to inflammatory and immune responses, have not been studied in gliomas, systematically. Methods RNA‑seq data and corresponding clinical information of glioma patients were collected from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA), and mRNA data of normal brain tissues were obtained in Genotype-Tissue Expression (GTEx) project. Wilcoxon test was performed to analyze the correlation of ITGAL expression and glioma subtypes. Univariate and multivariate cox proportional hazards regression, receiver operating characteristic (ROC) curves and Kaplan-Meier plots were used to evaluate the prognostic value of ITGAL in glioma. Functional enrichment analyses and immune infiltration analysis were performed to investigate the potential function in mediating the immune response in the tumor microenvironment. Finally, we evaluated the ability of ITGAL for predicting the efficacy of ICB treatment for patients. Results We found the up-regulation of ITGAL may predict a poor prognosis for glioma patients, the expression level increased with the increasing of WHO grade and 1p19q co-deletion status and IDH mutation status. The total methylation level and copy number variation of ITGAL were moderately correlated with its mRNA expression in LGG samples (P < 0.05). Furthermore, ITGAL was correlated with the immunosuppressive tumor microenvironment for the strong correlation with M2 macrophages and Tregs. Finally, GSEA showed the upregulation of ITGAL was mainly involved in the signal recognition and regulation between immune cells, and Toll-like receptor signaling pathway. Conclusion ITGAL is a novel tumor-related and immune-associated biomarker, which could predict the prognosis and effect of ICB therapy for glioma patients.