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

Purpose

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.