Integrated genome-wide DNA methylation and transcriptomic analysis prioritizes EPHA5 as a candidate non-invasive epigenetic biomarker for oral squamous cell carcinoma

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dc.authorid0000-0002-8066-8419
dc.authorid0000-0002-3753-7536
dc.authorid0000-0003-3951-0369
dc.authorid0000-0001-8544-955X
dc.authorid0000-0002-5101-8599
dc.authorid0000-0002-9241-8230
dc.authorid0000-0002-1627-1070
dc.authorid0000-0003-3967-8903
dc.authorid0000-0002-1957-6072
dc.authorid0000-0003-3885-1620
dc.authorid0000-0003-0905-6783
dc.authorid0000-0002-3339-1568
dc.authorid0000-0002-2152-8598
dc.authorid0000-0003-1479-3577
dc.contributor.authorDemokan, Semra
dc.contributor.authorÖzemek, Begüm
dc.contributor.authorTurna, Seval
dc.contributor.authorCömert, Sevde
dc.contributor.authorŞen, Cömert
dc.contributor.authorAvcı, Kağan
dc.contributor.authorÖzkan, Ahmet
dc.contributor.authorŞen, Sena
dc.contributor.authorPoda, Mehveş
dc.contributor.authorUlusan, Murat
dc.contributor.authorSezerman, Uğur
dc.contributor.authorAk, Gülsüm
dc.contributor.authorAlatlı, Fatma Canan
dc.contributor.authorDalay, Nejat
dc.date.accessioned2026-08-26T11:10:03Z
dc.date.available2026-08-26T11:10:03Z
dc.date.issued2026
dc.departmentFakülteler, Tıp Fakültesi, Cerrahi Tıp Bilimleri Bölümü, Tıbbi Patoloji Ana Bilim Dalı
dc.description.abstractPurpose: Oral squamous cell carcinoma (OSCC) remains a major clinical challenge because of delayed diagnosis and the lack of validated non-invasive biomarkers for OSCC detection. Epigenetic alterations during oral carcinogenesis represent promising biomarker candidates. This study aimed to prioritize clinically relevant epigenetic biomarkers and validate EPHA5 using an integrated genome-wide DNA methylation and transcriptomic approach. Experimental Design: Genome-wide DNA methylation and transcriptomic profiling were performed to identify epigenetically deregulated genes in OSCC. Candidate genes were prioritized by integrating DNA methylation, transcriptomic data and biological relevance. EPHA5 was subsequently selected for validation and evaluated by quantitative methylation-specific PCR (QMSP) and quantitative real-time PCR (QRT-PCR) in tissue, saliva and serum samples from independent cohorts comprising patients with OSCC, oral premalignant lesions (OPML) and healthy controls. Results: Genome-wide analysis identified 661 upregulated and 577 downregulated genes together with 2,431 differentially methylated regions corresponding to 1,776 genes. Integrated analysis generated a panel of 51 candidate genes, from which EPHA5 was prioritized using integrated DNA methylation, gene expression, pathway enrichment and biological relevance. EPHA5 promoter hypermethylation was detected in 66.7% of OSCC tumors, whereas concurrent promoter hypermethylation and reduced expression were observed in 28.6% of tumors. Methylation was also detected in 54.5% of OPML lesions and in the saliva of 47.6% of OSCC patients but was rarely detected in healthy controls. Tumor EPHA5 methylation significantly discriminated OSCC from healthy controls (AUC = 0.780, p = 0.004; sensitivity, 71.4%; specificity, 75%). Salivary EPHA5 methylation also significantly discriminated OSCC from healthy controls (AUC = 0.717, p = 0.025; sensitivity, 52.4%; specificity, 87.5%), whereas serum methylation showed no significant diagnostic utility (AUC = 0.571, p = 0.462). Discrimination between OSCC and OPML was limited and did not reach statistical significance (tumor AUC = 0.662, p = 0.068; salivary AUC = 0.600, p = 0.264). Conclusions: Frequent tumor hypermethylation together with detectable salivary methylation supports further evaluation of EPHA5 as a candidate non-invasive epigenetic biomarker for OSCC. However, its moderate diagnostic performance, limited discrimination between OSCC and OPML, and lack of external validation indicate that larger prospective studies and evaluation within multimarker methylation panels are required before clinical implementation.
dc.identifier.citationDemokan, S., Özemek, B., Turna, S., Cömert, S., Şen, C., Avcı, K., Özkan, A., Şen, S., Poda, M., Ulusan, M., Sezerman, U., Ak, G., Alatlı, F. C., & Dalay, N. (2026). Integrated genome-wide DNA methylation and transcriptomic analysis prioritizes EPHA5 as a candidate non-invasive epigenetic biomarker for oral squamous cell carcinoma. Frontiers in Oncology, https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1932336/abstract
dc.identifier.issn2234-943X
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2026.1932336/abstract
dc.identifier.urihttps://hdl.handle.net/20.500.13055/1609
dc.identifier.wosqualityQ2
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.indekslendigikaynak.otherSCI-E - Science Citation Index Expanded
dc.institutionauthorAlatlı, Fatma Canan
dc.institutionauthorid0000-0002-2152-8598
dc.language.isoen
dc.publisherFrontiers Media S. A.
dc.relation.ispartofFrontiers in Oncology
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectEphA5
dc.subjectEpigenetic Biomarker
dc.subjectGenome-Wide DNA Methylation
dc.subjectLiquid Biopsy
dc.subjectOral Premaliglant Lesion
dc.subjectOral Squamos Cell Carcinoma
dc.subjectSaliva
dc.subjectTranscriptomics
dc.titleIntegrated genome-wide DNA methylation and transcriptomic analysis prioritizes EPHA5 as a candidate non-invasive epigenetic biomarker for oral squamous cell carcinoma
dc.typeArticle
dspace.entity.typePublication

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