Effects of expression of DKK3 on the tumor immune response and prognosis in glioblastoma

Abstract

Purpose Recent work has demonstrated that Dickkopf-3 (DKK3) plays a crucial role in regulating the Wnt/β-catenin signaling pathway. In addition, the relationship between DKK3 and prognosis was mentioned in patients with glioblastoma (GBM). The aim of our study was to explain the correlation between DKK3 expression and Wnt/β-catenin pathway-related genes. Moreover, we investigated the different expressions of DKK3 on the tumor immune response in low-grade gliomas (grade Ⅱ-Ⅲ) and GBM (grade Ⅳ).

Methods Using data from The Cancer Genome Atlas (TCGA) program, we obtained clinicopathologic information from 515 low-grade gliomas and 525 glioblastomas. The relationship between clinical characteristics and Wnt/β-catenin pathway-related gene expression was assessed through Pearson's correlation analysis. Linear regression analysis also was performed to evaluate the association between DKK3 expression and immune cells.

Results Our study included 1,040 patients with glioma (grade Ⅱ-Ⅳ). As the grade increased, DKK3 and Wnt/β-catenin pathway-related genes showed significantly positive correlation. DKK3 had a weak effect on immunosuppression of low-grade gliomas, whereas, in GBM, DKK3 was involved in down-regulation of immunosuppression. Therefore, we hypothesized that the role of DKK3 would be different in low-grade gliomas and GBM.

Conclusions DKK3 has a weak effect in low-grade glioma, but significantly affects immunosuppression and poor prognosis in GBM. Therefore, we suggest that expression of DKK3 plays a different role between low-grade gliomas and GBM via the Wnt/β-catenin pathway.