Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, 333, Taiwan.
J Otolaryngol Head Neck Surg. 2012 Apr;41(2):94-101.
Inverted papilloma is associated with sinonasal squamous cell carcinoma. This study aimed to investigate the epigenetic regulation of the tumour suppressor gene DLEC1 in inverted papilloma and sinonasal squamous cell carcinoma.
DLEC1 gene expression was investigated by quantitative real-time polymerase chain reaction (QRT-PCR) in normal mucosa, inverted papilloma, and squamous cell carcinoma tissues. Methylation-specific PCR and subsequent autosequencing were also used to examine the methylation status of DLEC1 promoter and the involved mechanism. DLEC1 expression in a large validation set was evaluated by immunohistochemistry (n = 25 in each group).
DLEC1 was downregulated in inverted papilloma and squamous cell carcinoma tissues compared to normal mucosa (p < .01 in QRT-PCR and immunohistochemistry), with squamous cell carcinoma more repressed (p < .05 in QRT-PCR and immunohistochemistry) than inverted papilloma tissues. DLEC1 promoter hypermethylation was found in squamous cell carcinoma tissues.
Repression of DLEC1 in squamous cell carcinoma tissues is associated with promoter hypermethylation. DLEC1 is downregulated in sinonasal squamous cell carcinoma and inverted papilloma and has a distinct mechanism.
内翻性乳头状瘤与鼻腔鼻窦鳞状细胞癌相关。本研究旨在探讨肿瘤抑制基因 DLEC1 在鼻腔鼻窦内翻性乳头状瘤和鳞状细胞癌中的表观遗传调控。
通过实时定量聚合酶链反应(QRT-PCR)检测正常黏膜、内翻性乳头状瘤和鳞状细胞癌组织中 DLEC1 基因的表达。采用甲基化特异性 PCR 和自动测序进一步检测 DLEC1 启动子的甲基化状态及其相关机制。通过免疫组织化学(每组 25 例)评估 DLEC1 在大验证集中的表达。
与正常黏膜相比,内翻性乳头状瘤和鳞状细胞癌组织中 DLEC1 表达下调(QRT-PCR 和免疫组织化学均为 p <.01),且鳞状细胞癌组织下调更明显(QRT-PCR 和免疫组织化学均为 p <.05)。在鳞状细胞癌组织中发现 DLEC1 启动子高甲基化。
鳞状细胞癌组织中 DLEC1 的抑制与启动子高甲基化有关。DLEC1 在鼻腔鼻窦鳞状细胞癌和内翻性乳头状瘤中下调,其机制不同。