文章：

全基因组DNA甲基化分析证实增殖性疣状白斑中的口腔鳞状细胞癌为一种独特的口腔癌亚型：一项病例对照研究

Genome-Wide DNA Methylation Confirms Oral Squamous Cell Carcinomas in Proliferative Verrucous Leukoplakia as a Distinct Oral Cancer Subtype: A Case–Control Study

原文发布日期：13 January 2025

DOI: 10.3390/cancers17020245

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Oral cancers in patients with proliferative verrucous leukoplakia (PVL-OSCC) exhibit different clinical and prognostic outcomes from those seen in conventional oral squamous cell carcinomas (cOSSCs). The aim of the present study is to compare the genome-wide DNA methylation signatures in fresh frozen tissues between oral squamous cell carcinomas in patients with PVL and cOSCC using the Illumina Infinium MethylationEPIC BeadChip. Methods: This case–control study was carried out at the Stomatology and Maxillofacial Surgery Department of the General University Hospital of Valencia. For the epigenomic study, unsupervised exploratory bioinformatic analyses were performed using principal component and heatmap analysis. Supervised differential methylation analyses were conducted using a rank-based regression model and a penalized logistic regression model to identify potential prognostic biomarkers. Results: The unsupervised analyses of the global methylation profiles did not allow us to differentiate between the distinct oral cancer groups. However, the two supervised analyses confirmed the existence of two oral carcinoma phenotypes. We identified 21 differentially methylated CpGs corresponding to 14 genes. Among them, three CpGs had not been previously assigned to any known gene, and the remaining were associated with genes unrelated to oral cancer. The AGL, WRB, and ARL15 genes were identified as potential prognostic biomarkers. Conclusions: This study emphasizes the significant role of epigenetic dysregulation in OSCC, particularly in cases preceded by PVL. We have provided data on differential methylation genes that could be involved in the molecular carcinogenesis of PVL-OSCC.

摘要翻译： 

背景/目的：增殖性疣状白斑患者中的口腔癌（PVL-OSCC）在临床及预后方面与传统口腔鳞状细胞癌（cOSCC）存在差异。本研究旨在利用Illumina Infinium MethylationEPIC甲基化芯片，比较PVL相关口腔鳞状细胞癌与传统口腔鳞状细胞癌在新鲜冷冻组织中的全基因组DNA甲基化特征。方法：本病例对照研究在瓦伦西亚大学总医院口腔颌面外科开展。在表观基因组学分析中，采用主成分分析与热图分析进行无监督探索性生物信息学分析；同时运用基于排序的回归模型与惩罚逻辑回归模型进行有监督差异甲基化分析，以识别潜在的预后生物标志物。结果：全基因组甲基化谱的无监督分析未能有效区分不同口腔癌组别，但两种有监督分析均证实存在两种口腔癌表型。我们共鉴定出21个差异甲基化CpG位点，对应14个基因。其中3个CpG位点尚未被注释至任何已知基因，其余位点关联的基因均与口腔癌无已知关联。AGL、WRB和ARL15基因被确定为潜在的预后生物标志物。结论：本研究强调了表观遗传失调在口腔鳞状细胞癌（特别是PVL继发癌变病例）中的重要作用，并提供了可能参与PVL-OSCC分子致癌过程的差异甲基化基因数据。

原文链接：

Genome-Wide DNA Methylation Confirms Oral Squamous Cell Carcinomas in Proliferative Verrucous Leukoplakia as a Distinct Oral Cancer Subtype: A Case–Control Study