DNA methylation analysis of the epigenome in oral squamous cell carcinoma

TL;DR

This study analyzes DNA methylation patterns in oral squamous cell carcinoma to identify potential biomarkers and understand their role in cancer development.

Contribution

The study identifies ZNF880 as a hypermethylated gene in OSCC, linking its methylation to reduced gene expression and tumor progression.

Findings

OSCC tumor tissue showed 277,805 differential methylation probes, with 37.4% being hypermethylated.

ZNF880 was found to be highly methylated and expressed at lower levels in OSCC tissues compared to normal tissues.

Methylation changes were associated with pathways like PI3K-Akt signaling and cancer proteoglycan activity.

Abstract

Oral squamous cell carcinoma (OSCC) is one of the most common oral malignancies, which can occur in any part of the mouth and is highly malignant. DNA Methylation is an epigenetic modification of the genome, which is involved in key cellular processes and has a crucial impact on the occurrence, development, invasion and metastasis of tumors. In this study, we conducted a comprehensive analysis of DNA methylation characteristics in OSCC with the aim of identifying potential diagnostic epigenetic biomarkers and exploring possible mechanisms of methylation’s influence on OSCC.

In this study, genome-wide DNA methylation analysis was performed using Infinium Methylation EPIC arrays, including tumor tissue and adjacent non-tumor tissue from 12 OSCC patients. Differential methylation probes and regions (DMP/DMR) were identified for gene function analysis. Characteristic DMPs and genes were screened according to the specific situation, and OSCC-targeted methylation data from 25 patients in the validation cohort were used to further validate the differential methylation levels of our selected genes. Finally, the expression levels of methylated genes in OSCC were verified by combining RNA-Seq data with quantitative real-time polymerase chain reaction (qRT-PCR).

There were 277,805 DMPs in OSCC tumor tissue. Hypermethylated DMP accounted for 37.4% of all DMPs and hypomethylated DMPs was 62.6%. Functional pathway analysis showed that it was mainly related to passive transmembrane transporter activity, cancer proteoglycan and PI3K-Akt signaling pathway. The methylation level of ZNF880 was emphatically verified in the verification cohort, and the results showed that there was high methylation in ZNF880 in the verification cohort. Subsequently, through RNA-Seq data and qRT-PCR, it was confirmed that the expression of ZNF880 in OSCC tissues was significantly lower than that in normal tissues. This verified the correlation between the high methylation of ZNF880 and gene expression.

This study comprehensively reveals changes in genome-wide DNA methylation patterns in OSCC, indicating that abnormal hypermethylation of the ZNF880 gene plays a catalytic role in the pathogenesis of OSCC.

The online version contains supplementary material available at 10.1186/s40246-025-00899-3.

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