PATH-06. DNA METHYLATION PATTERNS AND IMMUNE MICROENVIRONMENT IN CYSTICGBM

Abstract

Abstract As a rare subtype of glioblastomas (GBM), genetic features in cystic GBM (cGBM) are still largely unknown. We have previously identified a series of active T cell subsets and positive cytokines/chemocytokines in the cystic fluid of cGBMs, including IFN-gamma, IL-2, IL-6, IL-8, TNF-alpha, and MIP-1alpha/beta. This study aimed to evaluate the prognosis of cGBM through DNA methylation patterns and immune microenvironment transcriptional signatures. IvyGAP, EGA and fresh samples from a prospective Chinese cohort were collected to investigate genomic signatures, immune microenvironment and survival outcomes in patients with cGBMs. Gd T1-weighted, T2-weighted, T2-Flair, DWI or ADC images were used to classify cGBM. 143 cases with MGMT/IDH record were used to compare survival time and genomic analysis. Among the three cohorts, Kaplan-Meier analysis showed cystic features have benefit to overall survival (OS). Moreover, cyst feature is the forth factor (HR=0.65, [95% CI 0.42, 1.01]) of survival after IDH, MGMT and Stupp therapeutic regimen. Interestingly, in IDH-wild/MGMT-unmethyled subtype, cGBM patients have longer OS vs noncystic GBM (noncGBM) patients (HR = 0.57, [95% CI 0.33, 0.99]). Compared to noncGBM, cGBM patients have hypomethylation state both in whole gene region and cpG islands. Ivygap database showed between cystic and noncystic group, in sub-structures such as CT (cellular tumor region), CTpan (pseudopalisading cells around necrosis) and CTpnz (perinecrotic zone) there are differential gene expressions and different enrichment pathways. GSEA analysis showed within cGBM group, many gene sets associated with immune function activation such as TRL1/2/3/7 and IFN pathways. These results suggest that cysts of GBM may be associated with hypomethylation status an activated immune microenvironment which is associated with longer survival and may define a unique subgroup of GBM with intrinsically different biology and prognosis.