Background:HOXA1is a prognostic marker and a potential predictive biomarker for radioresistance in head and neck tumors. Its overexpression has been associated with promoter methylation and a worse prognosis in oral squamous cell carcinoma (OSCC) patients. However, opposite outcomes are also described. The effect of the methylation of this gene on different gene regions, other than the promoter, remains uncertain. We investigated the methylation profile at different genomic regions ofHOXA1in OSCC and correlated differentially methylated CpG sites with clinicopathological data. Methods: TheHOXA1DNA methylation status was evaluated by analyzing data from The Cancer Genome Atlas and three Gene Expression Omnibus datasets. Significant differentially methylated CpG sites were considered with a |∆β| ≥ 0.10 and a Bonferroni-correctedp-value < 0.01. Differentially methylated CpGs were validated by pyrosequencing using two independent cohorts of 15 and 47 OSCC patients, respectively. Results: Compared to normal tissues, we found significantly higher DNA methylation levels in the 3′UTR region ofHOXA1in OSCC. Higher methylation levels in tumor samples were positively correlated with smoking habits and patients’ overall survival. Conclusions: Our findings suggest thatHOXA1gene body methylation is a promising prognostic biomarker for OSCC with potential clinical applications in patient monitoring.
背景：HOXA1是头颈部肿瘤的预后标志物，也是放射抵抗的潜在预测生物标志物。其过表达与口腔鳞状细胞癌（OSCC）患者的启动子甲基化和不良预后相关。然而，也有研究报道了相反的结果。除启动子外，该基因在不同基因区域的甲基化效应仍不明确。本研究探讨了OSCC中HOXA1不同基因组区域的甲基化谱，并将差异甲基化的CpG位点与临床病理数据进行了关联分析。 方法：通过分析癌症基因组图谱和三个基因表达综合数据库的数据，评估HOXA1的DNA甲基化状态。显著差异甲基化CpG位点的判定标准为|∆β| ≥ 0.10且经Bonferroni校正后的p值 < 0.01。采用焦磷酸测序技术，分别在15例和47例OSCC患者组成的两个独立队列中对差异甲基化CpG位点进行验证。 结果：与正常组织相比，我们发现OSCC中HOXA1基因3′UTR区域的DNA甲基化水平显著升高。肿瘤样本中较高的甲基化水平与吸烟习惯呈正相关，并与患者总生存期存在关联。 结论：我们的研究结果表明，HOXA1基因体甲基化是OSCC具有潜力的预后生物标志物，在患者监测方面具有潜在的临床应用价值。
HOXA13′UTR Methylation Is a Potential Prognostic Biomarker in Oral Squamous cell Carcinoma
肿瘤(癌症)患者之家