Correlation between lower balance of Th2 helper T-cells and expression of PD-L1/PD-1 axis genes enables prognostic prediction in patients with glioblastoma

Abstract

Common cancer treatments include radiation therapy, chemotherapy including molecular targeted drugs and anticancer drugs, and surgical treatment. Recent studies have focused on investigating the mechanisms by which immune cells attack cancer cells and produce immune tolerance-suppressing cytokines, as well as on their potential application in cancer immunotherapy. We conducted expression profiling of CD274 (PD-L1), GATA3, IFNG, IL12R, IL12RB2, IL4, PDCD1 (PD-1), PDCD1LG2 (PD-L2), and TBX21 (T-bet) using data of 158 glioblastoma multiforme (GBM) patients with clinical information available at The Cancer Genome Atlas. Principal component analysis of the expression profiling data was used to derive an equation for evaluating the status of Th1 and Th2 cells. GBM specimens were divided based on the median of the Th scores. The results revealed that Th1HighTh2Low and Th1LowTh2Low statuses indicated better prognosis than Th1HighTh2High, and were evaluated based on the downregulation of PD-L1, PD-L2, and PD-1. Furthermore, Th2Low divided based on the threshold, as well as CD274Low and PDCD1Low, were associated with good prognosis. In the Th2Low subgroup, 14 genes were identified as potential prognostic markers. Of these, SLC11A1Low, TNFRSF1BLow, and LTBRLow also indicated good prognosis. These results suggest that low Th2 balance and low activity of the PD-L1/PD-1 axis predict good prognosis in GBM. The set of genes identified in the present study could reliably predict survival in GBM patients and serve as useful molecular markers. Furthermore, this set of genes could prove to be novel targets for cancer immunotherapy.

Target amplicon exome-sequencing identifies promising diagnosis and prognostic markers involved in RTK-RAS and PI3K-AKT signaling as central oncopathways in primary central nervous system lymphoma

“…Functional gene annotation was performed using GOstat ( http://gostat.wehi.edu.au/ ) and The Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 ( https://david.ncifcrf.gov/ ) as described [ 43 ].…”

“…Somatic mutations and CNVs derived from 27 PCNSL specimens were clustered according to the mutation profiling per specimen using JMP built-in modules (SAS Institute, Inc., Tokyo, Japan) as described [ 43 ].…”

“…The Kaplan-Meier method was used to estimate survival distributions for each group with the log-rank test among subgroups using JMP built-in modules (SAS Institute Inc.) [ 43 ]. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated based on a logistic regression model with respect to clinical variables that were assessed by multivariate analysis with stepwise selection to compare groups.…”

MicroRNA signature constituted of miR-30d, miR-93, and miR-181b is a promising prognostic marker in primary central nervous system lymphoma

“…Predicted targets of miRNAs with the top 30 TargetScan context++ scores [30] were listed in tables. Functional GO annotation was performed using miRBase, GOstat (http://gostat.wehi.edu.au/), and DAVID (https://david.ncifcrf.gov/), as described [31].…”

miR-101, miR-548b, miR-554, and miR-1202 are reliable prognosis predictors of the miRNAs associated with cancer immunity in primary central nervous system lymphoma

“…The miRNAs targeting them were searched by TargetScanHuman 7.2. MicroRNAs were annotated using miRBase 22 (http://www.mirbase.org/) and their targets were surveyed using TargetScanHuman 7.2 (http://www.targetscan.org/vert_72/) with the TargetScan context++ scores (<-0.01) [33] on the Human GRCh38/hg38. Functional GO annotation was performed using miRBase and DAVID 6.8 (https://david.ncifcrf.gov/), as described [33].…”