Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Background: CD86 has great potential to be a new target of immunotherapy by regulating cancer immune response. However, it remains unclear whether CD86 is a friend or foe in lower-grade glioma (LGG).

Methods: The prognostic value of CD86 expression in pan-cancer was analyzed using Cox regression and Kaplan-Meier analysis with data from the cancer genome atlas (TCGA). Cancer types where CD86 showed prognostic value in overall survival and disease-specific survival were identified for further analyses. The Chinese Glioma Genome Atlas (CGGA) dataset were utilized for external validation. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and Immunohistochemistry (IHC) were conducted for further validation using surgical samples from Jiangsu Province hospital. The correlations between CD86 expression and tumor immunity were analyzed using the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, Tumor IMmune Estimation Resource (TIMER) database, and expressions of immune checkpoint molecules. Gene Set Enrichment Analysis (GSEA) was performed using clusterprofiler r package to reveal potential pathways.

Results: Pan-cancer survival analysis established CD86 expression as an unfavorable prognostic factor in tumor progression and survival for LGG. CD86 expression between Grade-II and Grade-III LGG was validated using qRT-PCR and WB. Additionally, CD86 expression in LGG with unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter was significantly higher than those with methylated MGMT (P<0.05), while in LGG with codeletion of 1p/19q it was significantly downregulated as opposed to those with non-codeletion (P<2.2*10-16). IHC staining validated that CD86 expression was correlated with MGMT status and X1p/19q subtypes, which was independent of tumor grade. Multivariate regression validated that CD86 expression acts as an unfavorable prognostic factor independent of clinicopathological factors in overall survival of LGG patients. Analysis of tumor immunity and GSEA revealed pivotal role of CD86 in immune response for LGG.

Conclusions: Integrated analysis shows that CD86 is an unfavorable prognostic biomarker in LGG patients. Targeting CD86 may become a novel approach for immunotherapy of LGG.