GHSR GENE METHYLATION IN NEOPLASTIC PROCESSES OF THE ORAL CAVITY

Abstract

Aberrant DNA-methylation patterns are recognised assensitive and specific hallmarks of early carcinogenesisand hold considerable promise for improving cancer diagnostics. Hyper-methylation of the growth-hormone secretagogue receptor gene (GHSR) has been linked to tumour invasiveness and poor prognosis in several malignancies, yet its role in oral neoplastic transformation remains unclear. Purpose of the study. To evaluatemethylation of exon 1 of the GHSR gene in oral squamous-cell carcinoma (OSCC), oral premalignant lesions and normal mucosa, and to assess its diagnostic utility.Research methods. Seventy-nine biopsy specimenswere analysed: 35 OSCC, 16 premalignant lesions and28 samples of healthy oral mucosa. Genomic DNA waspurified with the GeneJet Genomic DNA Purification Kit and bisulphite-converted using the EpiJet Bisulfite Conversion Kit. The target region of exon 1 of GHSR was amplified by multiplex TouchDown-PCR and quantified by pyrosequencing on a PyroMark Q96 MD platform.Statistical analysis employed Student’s t-test (STATISTICA6.1) with significance set at p < 0,01. Scientific novelty.Pronounced hypermethylation of GHSR was detected inOSCC samples (56,6 ± 20,4%), significantly exceeding levels in premalignant tissue (18,6 ± 6,3%; p ≤ 0,04) and normal mucosa (4,8 ± 1,1%; p ≤ 0,025). Diagnostic performance analysis revealed 99% sensitivity and 89% specificity for distinguishing OSCC from healthy tissue.Elevated GHSR methylation in premalignant lesions indicates an early epigenetic shift towards malignant transformation. Conclusions. Hypermethylation of exon1 of GHSR is an informative biomarker for malignantand premalignant processes in the oral cavity and could be incorporated into early-screening protocols and disease-progression monitoring. Implementation of GHSR methylation assays may enhance diagnostic accuracy and support personalised therapeutic approaches.