ArticleBiomarker research2021
The REASON score: an epigenetic and clinicopathologic score to predict risk of poor survival in patients with early stage oral squamous cell carcinoma.
Article in Biomarker research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- EphA2/SHP2/SOX8 Axis: A Novel Target for Regulation of Migration and Cetuximab Treatment Sensitivity in Oral Squamous Cell Carcinoma.Molecular carcinogenesis · 2026Article
- The potential and promise of natural antioxidants as epigenetic modulators in oral squamous cell carcinoma.Cancer chemotherapy and pharmacology · 2026Review
- EBF1 regulates sensory establishment in the cochlea by positioning the medial boundary of the prosensory domain and restricting proliferation of the sensory progenitor population.Development (Cambridge, England) · 2026Article
- Convergent Immune-Coagulation Programs Underlie Gastrointestinal Bleeding Risk in Portal Vein Tumor Thrombosis-Associated Hepatocellular Carcinoma and Portal Hypertension.Human mutation · 2026Article
- Lesion-specific oral microbiome signatures and predicted carcinogenic pathways in oral squamous cell carcinoma: a paired-site study in Pakistan.Journal of oral microbiology · 2026Article
- Optimization of methylation capture sequencing workflow in formalin fixed tissue from oral squamous cell carcinoma patients.Oral oncology · 2025Article
- Unravelling molecular mechanism of oral squamous cell carcinoma and genetic landscape: an insight into disease complexity, available therapies, and future considerations.Frontiers in immunology · 2025Review
- Upregulation ofEpigenetics · 2024Article
- Artificial intelligence-based epigenomic, transcriptomic and histologic signatures of tobacco use in oral squamous cell carcinoma.NPJ precision oncology · 2024Article
- Clinical validation of a saliva-based matrix metalloproteinase-1 rapid strip test for detection of oral cavity cancer.Biomedical journal · 2024Article
- Innovations in Molecular Biomarkers and Biomaterial-Based Immunotherapies for Head & Neck Cancer.Current surgery reports · 2024Review
- Epigenetic Regulation in Oral Squamous Cell Carcinoma Microenvironment: A Comprehensive Review.Cancers · 2023Review
- Exploring animal models in oral cancer research and clinical intervention: A critical review.Veterinary medicine and science · 2023Review
- Gene Expression Profiles of Methyltransferases and Demethylases Associated with Metastasis, Tumor Invasion, CpG73 Methylation, and HPV Status in Head and Neck Squamous Cell Carcinoma.Current issues in molecular biology · 2023Article
- "ThermoTRP" Channel Expression in Cancers: Implications for Diagnosis and Prognosis (Practical Approach by a Pathologist).International journal of molecular sciences · 2023Review
- Prognostic Value of CAV1 and CAV2 in Head and Neck Squamous Cell Carcinoma.Biomolecules · 2023Article
- The emerging role of MCPH1/BRIT1 in carcinogenesis.Frontiers in oncology · 2023Review
- Neurotrophin Pathway Receptors NGFR and TrkA Control Perineural Invasion, Metastasis, and Pain in Oral Cancer.Advanced biology · 2022Article
- Epigenome-wide gene-age interaction study reveals reversed effects ofFrontiers in oncology · 2022Article
- Risk Stratification in Oral Cancer: A Novel Approach.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
23 authors at 8 institutions in 1 country.
Funding
Abstract
backgroundOral squamous cell carcinoma (OSCC) is a capricious cancer with poor survival rates, even for early-stage patients. There is a pressing need to develop more precise risk assessment methods to appropriately tailor clinical treatment. Genome-wide association studies have not produced a viable biomarker. However, these studies are limited by using heterogeneous cohorts, not focusing on methylation although OSCC is a heavily epigenetically-regulated cancer, and not combining molecular data with clinicopathologic data for risk prediction. In this study we focused on early-stage (I/II) OSCC and created a risk score called the REASON score, which combines clinicopathologic characteristics with a 12-gene methylation signature, to predict the risk of 5-year mortality.
methodsWe combined data from an internal cohort (n = 515) and The Cancer Genome Atlas (TCGA) cohort (n = 58). We collected clinicopathologic data from both cohorts to derive the non-molecular portion of the REASON score. We then analyzed the TCGA cohort DNA methylation data to derive the molecular portion of the risk score.
results5-year disease specific survival was 63% for the internal cohort and 86% for the TCGA cohort. The clinicopathologic features with the highest predictive ability among the two the cohorts were age, race, sex, tobacco use, alcohol use, histologic grade, stage, perineural invasion (PNI), lymphovascular invasion (LVI), and margin status. This panel of 10 non-molecular features predicted 5-year mortality risk with a concordance (c)-index = 0.67. Our molecular panel consisted of a 12-gene methylation signature (i.e., HORMAD2, MYLK, GPR133, SOX8, TRPA1, ABCA2, HGFAC, MCPH1, WDR86, CACNA1H, RNF216, CCNJL), which had the most significant differential methylation between patients who survived vs. died by 5 years. All 12 genes have already been linked to survival in other cancers. Of the genes, only SOX8 was previously associated with OSCC; our study was the first to link the remaining 11 genes to OSCC survival. The combined molecular and non-molecular panel formed the REASON score, which predicted risk of death with a c-index = 0.915.
conclusionsThe REASON score is a promising biomarker to predict risk of mortality in early-stage OSCC patients. Validation of the REASON score in a larger independent cohort is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.