Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance.
Detection of promoter hypermethylation in salivary rinses as a biomarker for head and neck squamous cell carcinoma surveillance.
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DOI：
10.1158/1078-0432.ccr-11-0324
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发表时间：
2011-07-15
期刊：
影响因子：
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通讯作者：
Califano JA
中科院分区：
文献类型：
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作者：
Carvalho AL;Henrique R;Jeronimo C;Nayak CS;Reddy AN;Hoque MO;Chang S;Brait M;Jiang WW;Kim MM;Claybourne Q;Goldenberg D;Khan Z;Khan T;Westra WH;Sidransky D;Koch W;Califano JA
在头颈部鳞状细胞癌（HNSCC）和其他实体瘤中发现了抑癌基因启动子的高甲基化。我们通过实时定量甲基化特异性PCR（Q-MSP）评估了HNSCC患者治疗前唾液冲洗液中的这些变化。通过使用Q-MSP评估来自HNSCC患者的治疗前唾液DNA样品的超甲基化模式。靶肿瘤抑制基因启动子区的选择是基于先前描述高危人群受试者中HNSCC筛查组的研究。选择的基因是：DAPK、DCC、MINT-31、TIMP-3、p16、MGMT、CCNA 1。我们分析了61例HNSCC患者的队列。33名分析的患者（54.1%）显示唾液DNA中至少一个选定基因的甲基化。治疗前甲基化唾液DNA与肿瘤部位（P = 0.209）和临床分期（P = 0.299）均无显著相关性。然而，局部疾病控制和总生存率显着降低患者的高甲基化唾液冲洗（P = 0.010和P = 0.015，分别）。多变量分析证实，这种高甲基化模式仍然是局部复发（HR = 12.2; 95%CI = 1.8-80.6; P = 0.010）和总生存率（HR = 2.8; 95%CI = 1.2-6.5; P = 0.016）的独立预后因素。我们能够通过使用一组先前描述为在HNSCC中特异性甲基化的基因启动子来证实患者的HNSCC唾液中启动子高甲基化率升高。治疗前唾液DNA超甲基化的检测似乎可以预测局部复发和总生存率。这一发现有可能影响HNSCC患者的治疗和监测。
Hypermethylation of tumor suppressor gene promoters has been found in head and neck squamous carcinoma (HNSCC) and other solid tumors. We evaluated these alterations in pretreatment salivary rinses from HNSCC patients by using real-time quantitative methylation-specific PCR (Q-MSP). Pretreatment saliva DNA samples from HNSCC patients were evaluated for patterns of hypermethylation by using Q-MSP. Target tumor suppressor gene promoter regions were selected based on a previous study describing a screening panel for HNSCC in a high-risk population subjects. The selected genes were: DAPK, DCC, MINT-31, TIMP-3, p16, MGMT, CCNA1. We analyzed the panel in a cohort of 61 HNSCC patients. Thirty-three of the analyzed patients (54.1%) showed methylation of at least one of the selected genes in the saliva DNA. Pretreatment methylated saliva DNA was not significantly associated with tumor site (P = 0.209) nor clinical stage (P = 0.299). However, local disease control and overall survival were significantly lower in patients presenting hypermethylation in saliva rinses (P = 0.010 and P = 0.015, respectively). Multivariate analysis confirmed that this hypermethylation pattern remained as an independent prognostic factor for local recurrence (HR = 12.2; 95% CI = 1.8–80.6; P = 0.010) and overall survival (HR = 2.8; 95% CI = 1.2–6.5; P = 0.016). We were able to confirm an elevated rate of promoter hypermethylation in HNSCC saliva of patients by using a panel of gene promoters previously described as methylated specifically in HNSCC. Detection of hypermethylation in pretreatment saliva DNA seems to be predictive of local recurrence and overall survival. This finding has potential to influence treatment and surveillance of HNSCC patients.