关键词: Dickkopf-3 Disease progression Glioblastoma multiforme Lower grade glioma Survival Wnt/β-catenin signaling

Mesh : Humans beta Catenin / genetics Brain Neoplasms / pathology Glioblastoma / genetics pathology Glioma / genetics pathology Immunosuppression Therapy Prognosis Adaptor Proteins, Signal Transducing / genetics

来  源:   DOI:10.1186/s12883-023-03236-0   PDF(Pubmed)

Abstract:
OBJECTIVE: We previously reported that expression of dickkopf-3 (DKK3), which is involved in the Wnt/β-catenin pathway, is significantly associated with prognosis in patients with glioblastoma multiforme (GBM). The aim of this study was to compare the association of DKK3 with other Wnt/β-catenin pathway-related genes and immune responses between lower grade glioma (LGG) and GBM.
METHODS: We obtained the clinicopathological data of 515 patients with LGG (World Health Organization [WHO] grade II and III glioma) and 525 patients with GBM from the Cancer Genome Atlas (TCGA) database. We performed Pearson\'s correlation analysis to investigate the relationships between Wnt/β-catenin-related gene expression in LGG and GBM. Linear regression analysis was performed to identify the association between DKK3 expression and immune cell fractions in all grade II to IV gliomas.
RESULTS: A total of 1,040 patients with WHO grade II to IV gliomas were included in the study. As the grade of glioma increased, DKK3 showed a tendency to be more strongly positively correlated with the expression of other Wnt/β-catenin pathway-related genes. DKK3 was not associated with immunosuppression in LGG but was associated with downregulation of immune responses in GBM. We hypothesized that the role of DKK3 in the Wnt/β-catenin pathway might be different between LGG and GBM.
CONCLUSIONS: According to our findings, DKK3 expression had a weak effect on LGG but a significant effect on immunosuppression and poor prognosis in GBM. Therefore, DKK3 expression seems to play different roles, through the Wnt/β-catenin pathway, between LGG and GBM.
摘要:
目的:我们先前报道了dickkopf-3(DKK3)的表达,参与Wnt/β-catenin通路,与多形性胶质母细胞瘤(GBM)患者的预后显着相关。这项研究的目的是比较DKK3与其他Wnt/β-catenin途径相关基因以及低级胶质瘤(LGG)和GBM之间的免疫反应的相关性。
方法:我们从癌症基因组图谱(TCGA)数据库中获得了515例LGG(世界卫生组织[WHO]II级和III级胶质瘤)患者和525例GBM患者的临床病理数据。我们进行了Pearson相关分析,以探讨LGG和GBM中Wnt/β-catenin相关基因表达之间的关系。进行线性回归分析以确定所有II至IV级神经胶质瘤中DKK3表达与免疫细胞组分之间的关联。
结果:共有1,040例WHOII级至IV级胶质瘤患者纳入研究。随着胶质瘤的分级增加,DKK3显示出与其他Wnt/β-catenin途径相关基因的表达更强烈正相关的趋势。DKK3与LGG的免疫抑制无关,但与GBM的免疫反应下调有关。我们假设LGG和GBM之间DKK3在Wnt/β-catenin途径中的作用可能不同。
结论:根据我们的发现,DKK3的表达对LGG的影响较弱,但对GBM的免疫抑制和不良预后有显着影响。因此,DKK3的表达似乎扮演不同的角色,通过Wnt/β-catenin途径,LGG和GBM之间。
公众号