A Radiosensitivity Gene Signature and PD-L1 Status Predict ClinicalOutcome of Patients with Glioblastoma Multiforme in The CancerGenome Atlas Dataset / Journal of the Korean Cancer Association, 대한암학회지

ABSTRACT

Purpose@#Combination of radiotherapy and immune checkpoint blockade such as programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) blockade is being actively tested in clinicaltrial. We aimed to identify a subset of patients that could potentially benefit from this strategyusing The Cancer Genome Atlas (TCGA) dataset for glioblastoma (GBM). @*Materials and Methods@#A total of 399 cases were clustered into radiosensitive versus radioresistant (RR) groupsbased on a radiosensitivity gene signature and were also stratified as PD-L1 high versusPD-L1 low groups by expression of CD274 mRNA. Differential and integrated analyses withexpression and methylation data were performed. CIBERSORT was used to enumerate theimmune repertoire that resulted from transcriptome profiles. @*Results@#We identified a subset of GBM, PD-L1-high-RR group which showed worse survival comparedto others. In PD-L1-high-RR, differentially expressed genes (DEG) were highly enriched forimmune response and mapped into activation of phosphoinositide 3-kinase–AKT andmitogen-activated protein kinase (MAPK) signaling pathways. Integration of DEG and differentiallymethylated region identified that the kinase MAP3K8-involved in T-cell receptor signalingwas upregulated and BAI1, a factor which inhibits angiogenesis, was silenced.CIBERSORT showed that a higher infiltration of the immune repertoire, which included M2macrophages and regulatory T cells. @*Conclusion@#Taken together, PD-L1-high-RR group could potentially benefit from radiotherapy combinedwith PD-1/PD-L1 blockade and angiogenesis inhibition.