The overall survival of patients with lower grade glioma (LGG) varies greatly, but the current histopathological classification has limitations in predicting patients’ prognosis. Therefore, this study aims to find potential therapeutic target genes and establish a gene signature for predicting the prognosis of LGG. CD44 is a marker of tumor stem cells and has prognostic value in various tumors, but its role in LGG is unclear. By analyzing three glioma datasets from Gene Expression Omnibus (GEO) database, CD44 was upregulated in LGG. We screened 10 CD44-related genes via protein–protein interaction (PPI) network; function enrichment analysis demonstrated that these genes were associated with biological processes and signaling pathways of the tumor; survival analysis showed that four genes (CD44, HYAL2, SPP1, MMP2) were associated with the overall survival (OS) and disease-free survival (DFS)of LGG; a novel four-gene signature was constructed. The prediction model showed good predictive value over 2-, 5-, 8-, and 10-year survival probability in both the development and validation sets. The risk score effectively divided patients into high- and low- risk groups with a distinct outcome. Multivariate analysis confirmed that the risk score and status of IDH were independent prognostic predictors of LGG. Among three LGG subgroups based on the presence of molecular parameters, IDH-mutant gliomas have a favorable OS, especially if combined with 1p/19q codeletion, which further confirmed the distinct biological pattern between three LGG subgroups, and the gene signature is able to divide LGG patients with the same IDH status into high- and low- risk groups. The high-risk group possessed a higher expression of immune checkpoints and was related to the activation of immunosuppressive pathways. Finally, this study provided a convenient tool for predicting patient survival. In summary, the four prognostic genes may be therapeutic targets and prognostic predictors for LGG; this four-gene signature has good prognostic prediction ability and can effectively distinguish high- and low-risk patients. High-risk patients are associated with higher immune checkpoint expression and activation of the immunosuppressive pathway, providing help for screening immunotherapy-sensitive patients.
Excellent prognostic value of programmed death ligand 1 (PD-L1) is observed in patients with other cancers; however, the prognostic value of PD-L1 in glioblastoma (GBM) remains unclear. Therefore, this meta-analysis evaluated the prognostic value of PD-L1 in GBM. We performed a systematic search in databases to screen eligible articles. The hazard ratio (HR) and 95% confidence interval (95% CI) were extracted from included articles. This meta-analysis included 15 studies, and the forest plot indicated that increased PD-L1 expression was associated with poorer overall survival (OS) of GBM (HR, 1.16; 95% CI, 1.05–1.27; P = 0.002). Furthermore, stratified analysis confirmed that PD-L1 expression was associated with unfavorable OS at the protein level (HR, 1.30; 95% CI, 1.13–1.48; P < 0.001) and messenger ribonucleic acid (mRNA) level (HR, 1.05; 95% CI, 1.00–1.09; P = 0.041). The analysis of a dataset verified the prognostic value of PD-L1 and revealed an association between PD-L1 mRNA expression and the status of isocitrate dehydrogenase (IDH). In conclusion, increased PD-L1 expression predicts unfavorable OS in GBM and may be a promising prognostic biomarker of GBM.
Objective To investigate whether berberine can enhance the chemotherapeutic sensitivity of temozolomide to glioma cells and its mechanism. Methods CCK‐8 method was used to determine the effect of Ber and TMZ at different concentrations on glioma cell proliferation, and to evaluate the combined effect of Ber and TMZ. Flow cytometry was used to detect the effects of different concentrations of Ber, TMZ and the combination of the two on apoptosis and cell cycle of glioma cells. The expression of long non‐coding RNA (LncRNA) CASC‐2 in glioma cells was determined by RT‐PCR. Results CCK 8 determination results show that the single use of Ber (5, 10, 20, 40, 80, 160 umol/L) and TMZ (25, 50, 100, 200, 400, 800 umol/L) separate effect on gliomas are a dose dependent inhibition of glioma proliferation, and concentration of Ber for 40 umol/L on glioma U87 cells as well as a significant inhibition will not lead to a large number of cell death, so after the experiment we use 40 umol/L study on combination of Ber. After 40umol/L Ber was combined with TMZ at different concentrations, cell survival rate decreased significantly compared with TMZ alone at the same concentration. The cell cycle detection by flow cytometry showed that after the action of Ber combined with TMZ on glioma, glioma cells could be largely blocked in S phase and inhibited to enter the proliferation phase. The results of flow cytometry showed that after TMZ combined with Ber, the apoptosis rate of glioma cells significantly increased compared with TMZ alone. The results of RT‐PCR showed that the expression of CASC‐2 in the combination group was higher than that in the single group, and it was significantly higher than that before the treatment. Conclusion Berberine can sensitize TMZ to the effect of chemotherapy on glioma. Berberine can increase the sensitivity of glioma to TMZ by up‐regulating the expression of LncRNA CASC‐2 gene。
Review question / Objective: The purpose of this study was to explore the relationship between programmed cell death ligand 1 (PD-L1) expression and prognosis of glioblastoma (GBM) by meta-analysis, so as to provide evidence of Evidence-based medical for the treatment and prognosis of GBM.
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