Comparative profiling of immune genes improves the prognoses of lower grade gliomas

Objective:Lower grade gliomas(LGGs),classified as World Health Organization(WHO)grade II and grade III gliomas,comprise a heterogeneous group with a median survival time ranging from 4–13 years.Accurate prediction of the survival times of LGGs remains a major challenge in clinical practice.Methods:We reviewed the expression data of 865 LGG patients from 5 transcriptomics cohorts.The comparative profile of immune genes was analyzed for signature identification and validation.In-house RNAseq and microarray data from the Chinese Glioma Genome Atlas(CGGA)dataset were used as training and internal validation cohorts,respectively.The samples from The Cancer Genome Atlas(TCGA)and GSE16011 cohorts were used as external validation cohorts,and the real-time PCR of frozen LGG tissue samples(n=36)were used for clinical validation.Results:A total of 2,214 immune genes were subjected to pairwise comparison to generate 2,449,791 immune-related gene pairs(IGPs).A total of 402 IGPs were identified with prognostic values for LGGs.The HOXA9-related and CRH-related scores facilitated identification of patients with different prognoses.An immune signature based on 10 IGPs was constructed to stratify patients into low and high risk groups,exhibiting different clinical outcomes.A nomogram,combining immune signature,1p/19q status,and tumor grade,was able to predict the overall survival(OS)with c-indices of 0.85,0.80,0.80,0.79,and 0.75 in the training,internal validation,external validation,and tissue sample cohorts,respectively.Conclusions:This study was the first to report a comparative profiling of immune genes in large LGG cohorts.A promising individualized immune signature was developed to estimate the survival time for LGG patients.

ABCC8 is correlated with immune cell infiltration and overall survival in lower grade glioma

ATP binding cassette subfamily C member 8(ABCC8)encodes a protein regulating the ATP-sensitive potassium channel.Whether the level of ABCC8 mRNA in lower grade glioma(LGG)correlates with immune cell infiltration and patient outcomes has not been evaluated until now.Comparisons of ABCC8 expression between different tumors and normal tissues were evaluated by exploring publicly available datasets.The association between ABCC8 and tumor immune cell infiltration,diverse gene mutation characteristics,tumor mutation burden(TMB),and survival in LGG was also investigated in several independent datasets.Pathway enrichment analysis was conducted to search for ABCC8-associated signaling pathways.Through an online database,we found that ABCC8 expression in LGG was lower than in normal tissues.Then,the association of ABCC8 expression and immune cell infiltration in LGG was discussed.As we expected,the ABCC8 mRNA levels were negatively associated with non-T immune cell infiltration levels in all datasets.Consistently,TCGA_LGG RNA-seq data revealed that ABCC8 downregulated several non-T immune cell-associated signaling pathways in gene set enrichment analysis.Different ABCC8 expression groups showed diverse gene mutation characteristics and TMB.The high expression of ABCC8 was linked to improved survival of LGG patients.A pathway enrichment analysis of ABCC8-associated genes indicated that the GABAergic synapse signaling pathway might be involved in regulating immunity in LGG.Our findings show that ABCC8 reflects LGG tumor immunity and is an ideal prognostic biomarker for LGG.