Analysis of Gene Co-Expression Network to Identify the Role of CD8 + T Cell Infiltration-Related Biomarkers in High-Grade Glioma

Abstract

Background High-grade glioma is a type of heterogeneous lethal brain tumor most common in adults. At present, immune checkpoint inhibitors (ICIs) are being considered for first-line therapeutics for malignant GBM. Nonetheless, molecular markers for malignant GBM are unavailable at present. As a result, it is important to explore molecular markers related to immunity for GBM. Materials and Methods The present study adopted a deconvolution algorithm for quantifying immunocyte composition and measuring gene expression, and used weighted gene co-expression network analysis (WGCNA) to analyze GBM expression data obtained from Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and the Cancer Genome Atlas Glioblastoma Multiforme (TCGA-GBM) databases. Thereafter, key CD8+ T cell infiltration-related genes and modules were identified, and database analysis was conducted to verify the therapeutic and immune features of the selected genes. Results From this study, CD8+ T cell-related modules were identified. By using consistent clustering analysis, two panels of genes (red and green) with the highest correlation with CD8+ T cells infiltration were used to construct high-, low-expression groups, silent and/or mixed group of T cell infiltrations. In the high and low CD8+ T cell infiltration groups, a total of 535 differential genes were obtained, of which ten genes (RPS5, RPS6, FAU, RPS19, RPS23, RPS15A, RPS29, RPS14, RPS16, RPS27A) were identified through protein–protein interactions and co-expression network analysis. Post Cox regression and Kaplan–Meier (K-M) survival analysis, RPS5, RPS6, and RPS16 were selected as candidate prognostic biomarkers related to CD8+ T cells. Conclusion The three associated genes RPS5, RPS6, and RPS16 were markedly related to degree of T cell infiltration and immune-related activated. We identified their potential biomarkers and therapeutic targets associated with the extent of CD8+ T cell infiltration in GBM.

Targeted inhibition of RBPJ transcription complex alleviates the exhaustion of CD8+ T cells in hepatocellular carcinoma

“…Given the dependence of RBPJ transcriptional activity on NICD signaling, we hypothesized that the increased expression of target genes positively regulated by RBPJ in HCC-infiltrating CD8 + T cells were accompanied by the absence of RBPJ enrichment peaks in their promoters. RBPJ was significantly absent from the promoter of six T cell-associated genes ( Id2 8 , Rel 9 , Rps16 10 , Tpt1 11 , Rapgef6 12 , and Stat3 13 , collected from CellMarker database) (Fig. 2f ), among which Rps16 has been reported to regulate CD8 + T cell infiltration and function 10 .…”

“…RBPJ was significantly absent from the promoter of six T cell-associated genes ( Id2 8 , Rel 9 , Rps16 10 , Tpt1 11 , Rapgef6 12 , and Stat3 13 , collected from CellMarker database) (Fig. 2f ), among which Rps16 has been reported to regulate CD8 + T cell infiltration and function 10 . The RBPJ enrichment peaks at the Rps16 promoter in HCC were found to be decreased (Fig.…”

MRI histogram analysis of tumor-infiltrating CD8+ T cell levels in patients with glioblastoma

“…Furthermore, intratumoral CD8+ T cell infiltration is associated with better survival in patients with glioma ( Han et al, 2014 , Yang et al, 2010 ). Accordingly, there are intervention measures for promoting the dominance of CD8+ T cells in patients with GBM ( Feng et al, 2022 ). However, postoperative pathological examination remains the only assessment method for tumor-infiltrating CD8+ T cells.…”