研究动态
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表观遗传甲基化变化:作为口腔和颌面部肿瘤生物标志物的含义。

Epigenetic methylation changes: implication as biomarkers in oral and maxillofacial area cancers.

发表日期:2023 Jul
作者: Ovidiu Aghiorghiesei, Alexandra Iulia Irimie, Cornelia Braicu, Lajos Raduly, Andreea Nutu, Emilia Balint, Nikolay Mehterov, Boyan Vladimirov, Victoria Sarafian, Ondine Lucaciu, Radu Campian, Ioana Berindan-Neagoe
来源: Epigenetics & Chromatin

摘要:

鳞状细胞癌(SCC)是口腔颌面部头颈区最常见的癌症。对于口腔颌面部癌症的表观遗传变化亟需进行研究,因为观察到的变化可能具有关键的个性化医学诊断价值。本研究旨在鉴定SCC中最常见的高甲基化肿瘤抑制基因启动子,随后与患者生存率进行相关分析。我们评估了一组罗马尼亚(n=9)和保加利亚(n=12)患有口腔颌面部癌症的患者中22个肿瘤抑制基因启动子的甲基化状态。通过包含甲基化敏感和依赖甲基化的限制酶的EpiTect Methyl II PCR Array System对提取的DNA进行进一步消化,随后通过qPCR特异性扩增所得产物,并使用生产商提供的在线平台进行数据分析。观察到了不同的肿瘤抑制基因启动子的甲基化模式。其中,Cccnd2、Chd1、Cdh13、Cdkn1c、Neurog1、Gstp1和Runx3基因的甲基化谱与总体生存率进一步相关。我们的数据强调表观遗传变化对口腔颌面部癌症的临床异质性负有责任,并且显著影响患者的生存。需要对更大的患者群进行进一步研究以验证这些潜在的生物标志物。
Squamous cell carcinoma (SCC) is the most frequent cancer of the head and neck area in the oral cavity. Epigenetic alterations in oral and maxillofacial area cancers are urgently needed to be investigated, as the observed changes might have crucial diagnostic value for personalized medicine.Our study aimed to identify the most frequently hypermethylated tumor suppressor gene promoters in OSCC, followed by correlation analysis with the patients' survival. We evaluated the methylation status of the promoters in a panel of 22 tumor suppressor genes in Romanian (n=9) and Bulgarian (n=12) patient groups suffering from oral and maxillofacial area cancers. The extracted DNA was further digested through EpiTect Methyl II PCR Array System containing methylation-sensitive and methylation-dependent restriction enzymes, followed by specific amplification of the products obtained by qPCR and data analysis using the online platform provided by the producer.Different methylation patterns were observed in the tumor suppressor genes' promoters. Among them, the methylation profile of Cccnd2, Chd1, Cdh13, Cdkn1c, Neurog1, Gstp1, and Runx3 genes further correlated with overall survival rates.Our data emphasize that epigenetic alterations are responsible for the clinical heterogeneity of oral and maxillofacial area cancers and significantly impact on patient survival. Additional investigation on a larger patient cohort should validate these potential biomarkers.