ArticleCancer immunology, immunotherapy : CII2022
High DKK3 expression related to immunosuppression was associated with poor prognosis in glioblastoma: machine learning approach.
Article in Cancer immunology, immunotherapy : CII, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 20 citations in OpenAlex.
- Systems biology of Wnt signaling in glioma chemotherapy resistance: Integrating multi-omics mechanisms and emerging therapeutic vulnerabilities (Review).Oncology letters · 2026Review
- Wnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis.Signal transduction and targeted therapy · 2026Article
- Artificial Intelligence-Assisted Drug and Biomarker Discovery for Glioblastoma: A Scoping Review of the Literature.Cancers · 2025Review
- Identification and validation of immune-related and inflammation-related genes in endometriosis.Frontiers in endocrinology · 2025Article
- A Synopsis of Biomarkers in Glioblastoma: Past and Present.Current issues in molecular biology · 2024Review
- Significant Genes Associated with Mortality and Disease Progression in Grade II and III Glioma.Biomedicines · 2024Article
- Quantified pathway mutations associate epithelial-mesenchymal transition and immune escape with poor prognosis and immunotherapy resistance of head and neck squamous cell carcinoma.BMC medical genomics · 2024Article
- The Multifaceted Role of Human Dickkopf-3 (DKK-3) in Development, Immune Modulation and Cancer.Cells · 2023Review
- DKK3 expression is associated with immunosuppression and poor prognosis in glioblastoma, in contrast to lower-grade gliomas.BMC neurology · 2023Article
- The genes significantly associated with an improved prognosis and long-term survival of glioblastoma.PloS one · 2023Article
- Review
- Identification of genes from ten oncogenic pathways associated with mortality and disease progression in glioblastoma.Frontiers in oncology · 2022Article
- Immune-related gene signature to predict TACE refractoriness in patients with hepatocellular carcinoma based on artificial neural network.Frontiers in genetics · 2022Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundGlioblastoma multiforme (GBM) is an aggressive malignant primary brain tumor. Wnt/β-catenin is known to be related to GBM stemness. Cancer stem cells induce immunosuppressive and treatment resistance in GBM. We hypothesized that Wnt/β-catenin-related genes with immunosuppression could be related to the prognosis in patients with GBM.
methodsWe obtained the clinicopathological data of 525 patients with GBM from the brain cancer gene database. The fraction of tumor-infiltrating immune cells was evaluated using in silico flow cytometry. Among gene sets of Wnt/β-catenin pathway, Dickkopf-3 (DKK3) gene related to the immunosuppressive response was found using machine learning. We performed gene set enrichment analysis (GSEA), network-based analysis, survival analysis and in vitro drug screening assays based on Dickkopf-3 (DKK3) expression.
resultsIn analyses of 31 genes related to Wnt/β-catenin signaling, high DKK3 expression was negatively correlated with increased antitumoral immunity, especially CD8 + and CD4 + T cells, in patients with GBM. High DKK3 expression was correlated with poor survival and disease progression in patients with GBM. In pathway-based network analysis, DKK3 was directly linked to the THY1 gene, a tumor suppressor gene. Through in vitro drug screening, we identified navitoclax as an agent with potent activity against GBM cell lines with high DKK3 expression.
conclusionsThese results suggest that high DKK3 expression could be a therapeutic target in GBM. The results of the present study could contribute to the design of future experimental research and drug development programs for GBM.
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