Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Int J Cancer. 2010 Nov 15;127(10):2351-9. doi: 10.1002/ijc.25248.
Silencing of tumor suppressor genes plays a vital role in head and neck carcinogenesis. In this study, we aimed to evaluate to the utility of aberrant promoter hypermethylation for detection in a panel of 10 genes (KIF1A, EDNRB, CDH4, TERT, CD44, NISCH, PAK3, VGF, MAL and FKBP4) in head and neck squamous cell carcinoma (HNSCC) via a candidate gene approach. We investigated methylation of the gene promoters by bisulfite modification and quantitative methylation-specific PCR (Q-MSP) in a preliminary study of a limited cohort of salivary rinses from healthy subjects (n = 61) and patients with HNSCC (n = 33). The methylation status of 2 selected genes (EDNRB and KIF1A) were then analyzed in 15 normal mucosa samples from a healthy population, 101 HNSCC tumors and the corresponding salivary rinses from 71 out of the 101 HNSCC patients were collected before treatment. The promoter regions of CDH4, TERT, VGF, MAL, FKBP4, NISCH and PAK3 were methylated in normal salivary rinses while no methylation of CD44 was observed in either normal salivary rinses or tumor samples. However, KIF1A and EDNRB were methylated in 98 and 97% of primary HNSCC tissues respectively and were only methylated in 2 and 6.6% of normal salivary rinses. In addition, KIF1A and EDNRB were methylated in 38 and 67.6% of salivary rinses from HNSCC patients, respectively. Promoter hypermethylation of KIF1A and EDNRB is a frequent event in primary HNSCC, and these genes are preferentially methylated in salivary rinses from HNSCC patients. KIF1A and EDNRB are potential biomarkers for HNSCC detection.
肿瘤抑制基因的沉默在头颈部肿瘤发生中起着至关重要的作用。在这项研究中，我们旨在通过候选基因方法评估在一组 10 个基因（KIF1A、EDNRB、CDH4、TERT、CD44、NISCH、PAK3、VGF、MAL 和 FKBP4）中异常启动子高甲基化检测的应用。我们通过亚硫酸氢盐修饰和定量甲基化特异性 PCR（Q-MSP）在初步研究中检测了唾液冲洗液中这些基因启动子的甲基化情况，研究对象为健康受试者（n=61）和头颈部鳞状细胞癌（HNSCC）患者（n=33）的有限队列。然后，在 15 个来自健康人群的正常黏膜样本、101 个 HNSCC 肿瘤以及 71 个 HNSCC 患者中 101 个肿瘤相应的唾液冲洗液中分析了 2 个选定基因（EDNRB 和 KIF1A）的甲基化状态。CDH4、TERT、VGF、MAL、FKBP4、NISCH 和 PAK3 的启动子区域在正常唾液冲洗液中发生甲基化，而 CD44 无论是在正常唾液冲洗液还是肿瘤样本中均未发生甲基化。然而，KIF1A 和 EDNRB 在 98%和 97%的原发性 HNSCC 组织中分别发生甲基化，仅在 2%和 6.6%的正常唾液冲洗液中发生甲基化。此外，KIF1A 和 EDNRB 在 HNSCC 患者的唾液冲洗液中分别有 38%和 67.6%发生甲基化。KIF1A 和 EDNRB 的启动子高甲基化是原发性 HNSCC 的常见事件，并且这些基因在 HNSCC 患者的唾液冲洗液中优先发生甲基化。KIF1A 和 EDNRB 是 HNSCC 检测的潜在生物标志物。
