Abstract Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.

中文翻译：

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HPV阴性口腔和口咽鳞状细胞癌中DAPK、MGMT和RUNX3的高甲基化状态

摘要 口腔和口咽部鳞状细胞癌是世界上第六大最常见的癌症类型。在肿瘤发生过程中，基因启动子高甲基化被认为是抑癌基因转录沉默的重要机制，如 DAPK、MGMT 和 RUNX3。这些基因参与与细胞凋亡、DNA 修复和增殖相关的信号通路，其表达的丧失可能与癌症的发展和进展有关。为了研究高甲基化与临床病理和预后参数之间的关联，使用甲基化特异性 PCR 在 72 例 HPV 阴性口腔和口咽肿瘤中评估了启动子甲基化。DAPK、MGMT 和 RUNX3 的高甲基化频率分别为 38.88%、19.44% 和 1.38%。与没有甲基化的患者相比，具有 MGMT 高甲基化的患者具有更好的 2 年总生存率。由于 MGMT 是烷化剂的修复基因，它可以作为顺铂化疗候选者治疗反应的生物标志物，预测耐药性。鉴于癌细胞中相当高的超甲基化水平以及 MGMT 的预后相关性，DAPK 和 MGMT 显示出作为表观遗传标志物的潜力，其他研究可能会测试其在临床管理中的可行性和有效性。