ArticleBMC cancer2015
NDN and CD1A are novel prognostic methylation markers in patients with head and neck squamous carcinomas.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 2 syntheses or guidelines pooled it, 24 citations in OpenAlex.
- Portrait of DNA methylated genes predictive of poor prognosis in head and neck cancer and the implication for targeted therapy.Scientific reports · 2021Pooled it
- DNA methylation biomarkers in peripheral blood of patients with head and neck squamous cell carcinomas. A systematic review.PloS one · 2020Pooled it
- Soy Isoflavone Supplementation Increases Long Interspersed Nucleotide Element-1 (LINE-1) Methylation in Head and Neck Squamous Cell Carcinoma.Nutrition and cancer · 2019Trial
- Prognostic value of DNA methylation in head and neck cancer: a systematic review and meta-analysis.Translational cancer research · 2026Article
- Genome-wide DNA methylation profiling of HPV-negative leukoplakia and gingivobuccal complex cancers.Clinical epigenetics · 2023Article
- The Epigenesis of Salivary Glands Carcinoma: From Field Cancerization to Carcinogenesis.Cancers · 2023Review
- Prognostic and therapeutic prediction by screening signature combinations from transcriptome-methylome interactions in oral squamous cell carcinoma.Scientific reports · 2022Article
- Necdin, one of the important pathway proteins in the regulation of osteosarcoma progression by microRNA-200c.Bioengineered · 2022Article
- Epigenetic Regulations of Perineural Invasion in Head and Neck Squamous Cell Carcinoma.Frontiers in genetics · 2022Review
- Novel immune-related signature for risk stratification and prognosis in prostatic adenocarcinoma.Cancer science · 2021Article
- Epigenetic Modifications in Head and Neck Cancer.Biochemical genetics · 2020Review
- Article
- IRX-2 natural cytokine biologic for immunotherapy in patients with head and neck cancers.OncoTargets and therapy · 2018Review
- DNA methylation-based variation between human populations.Molecular genetics and genomics : MGG · 2017Review
- Focusing the management of rectal cancer.Annals of translational medicine · 2016Article
- Individualized risk prediction of outcomes for oral cavity cancer patients.Oral oncology · 2016Article
- Multiple imputation of missing covariates for the Cox proportional hazards cure model.Statistics in medicine · 2016Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundHPV-associated HNSCCs have a distinct etiologic mechanism and better prognosis than those with non-HPV associated HNSCCs. However, even within the each group, there is heterogeneity in survival time. Here, we test the hypothesis that specific candidate gene methylation markers (CCNA1, NDN, CD1A, DCC, p16, GADD45A) are associated with tumor recurrence and survival, in a well-characterized, prospective, cohort of 346 HNSCC patients.
methodsKaplan-Meier curves were used to estimate survival time distributions. Multivariable Cox Proportional Hazards models were used to test associations between each methylation marker and OST/RPFT after adjusting for known or identified prognostic factors. Stratified Cox models included an interaction term between HPV and methylation marker to test for differences in the associations of the biomarker with OST or RPFT across HPV status.
resultsMethylation markers were differentially associated with patient characteristics. DNA hypermethylation of NDN and CD1A was found to be significantly associated with overall survival time (OST) in all HNSCC patients (NDN hazard ratio (HR): 2.35, 95% CI: 1.40-3.94; CD1A HR: 1.31, 95% CI: 1.01-1.71). Stratification by HPV status revealed hypermethylation of CD1A was associated with better OST and recurrence/persistence-free time (RPFT) (OST HR: 3.34, 95% CI: 1.88-5.93; RPFT HR: 2.06, 95% CI: 1.21-3.49), while hypomethylation of CCNA1 was associated with increased RPFT in HPV (+) patients only (HR: 0.31, 95% CI: 0.13-0.74).
conclusionsThis study is the first to describe novel epigenetic alterations associated with survival in an unselected, prospectively collected, consecutive cohort of patients with HNSCC. DNA hypermethylation of NDN and CD1A was found to be significantly associated with increased overall survival time in all HNSCC patients. However, stratification by the important prognostic factor of HPV status revealed the immune marker, CD1A, and the cell cycle regulator, CCNA1 to be associated with prognosis in HPV (+) patients, specifically. Here, we identified novel methylation markers and specific, epigenetic molecular differences associated with HPV status, which warrant further investigation.
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