ArticleClinical oral investigations2017
Prognostic significance of the methylation of Wnt pathway antagonists-CXXC4, DACT2, and the inhibitors of sonic hedgehog signaling-ZIC1, ZIC4, and HHIP in head and neck squamous cell carcinomas.
Article in Clinical oral investigations, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Integrative multi-cohort analysis of DNA methylation profiles for pancreatic ductal adenocarcinoma biomarker discovery and prognosis.Frontiers in bioinformatics · 2026Article
- Epigenetic profiling reveals key super-enhancer networks driving oncogenesis in HPV-positive HNSCC.iScience · 2025Article
- The multifaceted roles of ZIC genes in cancer: from development regulators to cancer modulators.Discover oncology · 2025Review
- Identifying targeted cell-free DNA methylation regions in head and neck cancer via paired methylome analysis.Research square · 2024Article
- Epigenetic silencing of ZIC4 unveils a potential tumor suppressor role in pediatric choroid plexus carcinoma.Scientific reports · 2024Article
- Unravelling the Mysteries of the Sonic Hedgehog Pathway in Cancer Stem Cells: Activity, Crosstalk and Regulation.Current issues in molecular biology · 2024Review
- Review
- WNT5A, β‑catenin and SUFU expression patterns, and the significance of microRNA deregulation in placentas with intrauterine growth restriction.Molecular medicine reports · 2023Article
- Age-Related DNA Methylation in Normal Kidney Tissue Identifies Epigenetic Cancer Risk Susceptibility Loci in the ANKRD34B and ZIC1 Genes.International journal of molecular sciences · 2022Article
- An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy.The Journal of experimental medicine · 2022Article
- Article
- MicroRNA-221 promotes tumor progression by targeting HHIP in human glioblastoma.Translational cancer research · 2021Article
- Zinc finger of the cerebellum 5 promotes colorectal cancer cell proliferation and cell cycle progression through enhanced CDK1/CDC25c signaling.Archives of medical science : AMS · 2021Article
- An mRNA characterization model predicting survival in patients with invasive breast cancer based on The Cancer Genome Atlas database.Cancer biomarkers : section A of Disease markers · 2021Article
- Head and Neck Squamous Cell Carcinoma: Epigenetic Landscape.Diagnostics (Basel, Switzerland) · 2020Review
- Chromatin structure regulates cancer-specific alternative splicing events in primary HPV-related oropharyngeal squamous cell carcinoma.Epigenetics · 2020Article
- Integrative analysis of DNA methylation and gene expression in papillary renal cell carcinoma.Molecular genetics and genomics : MGG · 2020Article
- The Role of Sonic Hedgehog Signaling in the Tumor Microenvironment of Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2019Article
- Inhibition of miR‑194 suppresses the Wnt/β‑catenin signalling pathway in gastric cancer.Oncology reports · 2018Article
- hTERT promoter methylation status in peripheral blood leukocytes as a molecular marker of head and neck cancer progression.Journal of applied genetics · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesAberrations in Wnt and Shh signaling pathways are related to the pathogenesis of head and neck carcinomas, and their activation frequently results from epigenetic alterations. This study aimed to assess the frequency of methylation of negative regulators of Wnt signaling: CXXC4, DACT2, HDPR1, and FBXW11 and Shh signaling: HHIP, PTCH1, SUFU, ZIC1, and ZIC4 and correlate it with clinicopathological features in this group of patients. MATERIALS AND
methodsMethylation-specific PCR was used to detect gene promoter methylation, and real-time PCR was used to assess gene expression level.
resultsThe analysis of the occurrence of gene promoter methylation in head and neck carcinoma cell lines indicated that CXXC4, DACT2, HHIP, ZIC1, and ZIC4 are methylated in these tumors. These genes were further analyzed in tumor sections from oral and laryngeal cancer patients. Gene methylation rate was higher in laryngeal tumors. The methylation index in tumor samples correlated with the overall survival in a subgroup of oral cancer patients who died of the disease. Moreover, ZIC4 methylation correlated with lymph node involvement in oral cancer patients.
conclusionsOur findings corroborate that the activation of Wnt signaling in head and neck squamous cell carcinoma (HNSCC) is related to epigenetic silencing of its negative regulators. Moreover, the results indicate that the same mechanism of activation may operate in the case of Shh signaling. CLINICAL RELEVANCE: The methylation of ZIC4 may be considered a new prognostic marker in oral cavity and oropharyngeal tumors. Further investigations should determine the diagnostic significance of methylation of ZIC4, HHIP, and DACT2 in head and neck carcinomas.
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