ArticleCancer biomarkers : section A of Disease markers2022
Salivary DNA methylation markers for cancer of oral cavity.
Article in Cancer biomarkers : section A of Disease markers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 5 citations in OpenAlex.
- Article
- Emerging Diagnostic Strategies for Oral Cancer and Oral Potentially Malignant Disorders: A PRISMA-Guided Scoping Review.Diagnostics (Basel, Switzerland) · 2026Review
- Application of artificial intelligence in oral potentially malignant disorders: current opinions and future barriers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Overexpression and clinicopathological significance of zinc finger protein 71 in hepatocellular carcinoma.World journal of hepatology · 2025Article
- Decoding oral leukoplakia: microbiome dysbiosis and inflammatory dynamics unveiled in a rat model.Frontiers in microbiology · 2025Article
- Salivary Biomarkers and Their Link to Oncogenic Signaling Pathways in Oral Squamous Cell Carcinoma: Diagnostic and Translational Perspectives in a Narrative Review.Oncology research · 2025Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeAberrant DNA methylation plays a crucial role in oral carcinogenesis. Our previous study demonstrated hypermethylation of DAPK1, LRPPRC, RAB6C, and ZNF471 promoters in patients with tongue squamous cell carcinoma compared with normal samples. Methylation profiling using salivary DNA is considered a non-invasive alternative to tissue samples. Hence, the present study tested the DNA methylation status of these four promoters as indicators of oral cancer progression.
methodsWe performed the bisulfite-based targeted next-generation sequencing of four candidate genes in saliva and tissue DNA from normal, premalignant, and squamous cell carcinoma subjects. The clinicopathological association, diagnostic, and prognostic utility of aberrant DNA methylation were evaluated using the TCGA-HNSCC dataset. Using the Xgboost algorithm and logistic regression, CpG sites were prioritized, and Receiver Operating Characteristic was generated. By Log-rank test and Kaplan-Meier (KM) curves, an association between methylation and overall survival (OS), disease-free interval (DFI), and progression-free interval (PFI) were computed.
resultsWe identified all four genes as significantly hypermethylated in premalignant and malignant samples compared with normal samples. The methylation levels were comparable between saliva and tissue samples with an r-value of 0.6297 to 0.8023 and 0.7823 to 0.9419 between premalignant tissue vs. saliva and OC vs. saliva, respectively. We identified an inverse correlation between DAPK1, LRPPRC, RAB6C, and ZNF471 promoter methylation with their expression. A classifier of 8 differentially methylated CpG sites belonging to DAPK1, RAB6C, and ZNF471 promoters was constructed, showing an AUC of 0.984 to differentiate tumors from normal samples. The differential methylation status of DAPK1, LRPPRC, and ZNF71 promoters was prognostically important. Abnormal expression of all four genes was associated with immune infiltration.
conclusionsThus, methylation analysis of these candidate CpG sites from saliva can be helpful as a non-invasive tool for the clinical management of OC.
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