The EGFR path regulates the effect of CSN6 and PD-L1 expression on GBM prognosm.

Glioblastoma (GBM) is the most common adult malignant brain tumor.
In recent years, programmed death-1/programmed death lilog 1 (PD-1/PD-L1) immuno-checkpoint inhibitors have changed the treatment patterns of many tumors and achieved some efficacy in GBM therapy, however, the relationship between over-expression and prognosis of GBM,PD-L1 is still controversial.
study found that COP9 signaling small body 6 (CSN6) is essential to maintain tumor cell protein stability, in GBM, CSN6 over-expression is associated with tumor progression, and EGFR-ERK signaling pathrapies regulate CSN6 expression.
, Lingrui Su of the Pathology Laboratory of the Second Hospital affiliated with Hebei Medical University, found that GBM's EGFR-ERK pathology regulates CSN6 to promote stable expression of PD-L1.
results were published online March 2020 in Molecular Carcinogenesis.
research method Analysis of glioma data from the Cancer Genome Atlas (TCGA) shows that EGFR, CSN6, and PD-L1 mRNA levels in GBM are higher than those of astromas (P<0.05).
Kaplan-Meier survival analysis showed a negative correlation between EGFR, CSN6, and PD-L1 expression levels and total patient survival rate (OS) (P<0.05).
immunogroupization (IHC) staining results from clinical tumor samples were found to show high expression (P<0.05) in asstar cell tumors and EGFR, CSN6, and PD-L1 in GBM compared to normal brain tissue, while the expression level of GBM was significantly higher than that of asbestoblastoma (P<05).
Kaplan-Meier survival analysis showed a significant decrease in OS (P<05) in patients with high expression of EGFR, CSN6, and PD-L1.
indicates a poor prognostic prognosticity in highly expressed GBM patients with PD-L1.
IHC staining results showed that PD-L1 expression levels in 47 GBM patients showed a significant negative correlation with cd8-positive T-cell immersion (r=0.5064; P=0.0003), indicating that high expression of PD-L1 in GBM may inhibit CD8-positive T cell immersion.
Kaplan-Meier analysis showed a relatively poor prognostic prognosticity (P<0.05) in GBM patients with high expression of PD-L1 and reduced CD8-positive T-cell immersion.
, patients with low expression of PD-L1 and high levels of CD8-positive T cell immersion had relatively good prognosis (P<0.05).
, PD-L1 inhibitors may be an effective immunotherapy solution for GBM.
immunofluorescent staining results from clinical tumor samples showed that in 5 tumor samples, CSN6 and EGFR were expressed together with PD-L1, and the percentages of EGFR and CSN6 double-positive cells were 75% and 85%, respectively.
IHC staining results of EGFR, CSN6 and PD-L1 in 47 GBM patients were found to be significantly positively related to PD-L1 expression (r=0.6539; P<0.001).
addition, CSN6 is significantly positively related to EGFR (r=0.6300; P<0.001) and PD-L1 expression (r=0.8168; P<0.001).
that the EGFR path may play a key role in regulating CSN6 and PD-L1 expressions.
in-body experiments, it was found that when using skin growth factor (EGF) to treat U87 and U251 GBM cell line, EGF (100-300ng/mL) was observed to raise p-EGFR, p Expressions of -ERK, CSN6, and PD-L1 (P<0.05), and the expression levels of CSN6 and PD-L1 increase significantly as the EGF processing time increases (P<0.05).
ERK signal path blocker PD98059 inhibits the EGF from raising the role of CSN6 and PD-L1.
, the EGF activates the ERK path and raises the expression of CSN6 and PD-L1.
researchers used siRNA to knock down CSN6, the effect of EGF upward PD-L1 (P<0.05) was significantly reduced.
, CSN6 can partially reduce the total expression of EGFR and p-EGFR (P<0.05).
treatment of GBM cells with EGF and protein synthesis inhibitor cyclohexamine (CHX) found that EGF reduced CSN6 and PD-L1 protein turnover (P<0.05) caused by CHX. Protease inhibitor MG132 inhibits CSN6-mediated PD-L1 reduction (P<0.05) and inhibits CSN6 to increase CHIP expression (P<0.05).
above data show that in GBM, the EGFR-ERK path is up PD-L1 because CSN6 promotes its stability.
The study showed that in GBM, high expression of EGFR, CSN6 and PD-L1 was associated with poor prognosticity, and the main mechanism may be that PD-L1 over-expression led to a decrease in cd8-positive T cell immersion.
EGFR, CSN6 and PD-L1 expressions in GBM were positively related.
in-body experiments have found that the EGFR-ERK path is activated in GBM cells to increase CSN6 expression, thus promoting the maintenance of PD-L1 protein stability.
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