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DcR1、DcR2、DR4、DR5 基因启动子高甲基化与舌鳞癌的临床意义。

Hypermethylation of DcR1, DcR2, DR4, DR5 gene promoters and clinical significance in tongue carcinoma.

机构信息

Department of stomatology, Guangzhou Huadu District Maternal and Child Health Hospital; Affiliated Guangzhou Huadu Hospital of Guangdong Medical University, China.

Department of medical imaging,Guangzhou Huadu District Maternal and Child Health Hospital; Affiliated Guangzhou Huadu Hospital of Guangdong Medical University, China.

出版信息

Am J Otolaryngol. 2019 Nov-Dec;40(6):102258. doi: 10.1016/j.amjoto.2019.07.002. Epub 2019 Jul 2.

Abstract

OBJECTIVE

Tongue squamous cell carcinoma (TSCC) is one of the most common malignancies in the oral cavity, and its incidence and mortality have been constantly increasing these years. A large number of tumor suppressor genes are involved in the development of the TSCC and it has been reported that the aberrant hypermethylation of tumor suppressor genes may play a key role in the process of the TSCC. In this study, we sought to analyze the association of methylation of DcR1, DcR2, DR4 and DR5 gene promoters and clinical significance in the TSCC to evaluate association between methylation of DcR1, DcR2, DR4 and DR5 gene and Clinical Significance in tongue squamous cell carcinoma.

METHODS

Methylation-specific PCR(MSP) was used to analyze the methylation of the promoters of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) receptors in 45 TSCC cases. Real-Time PCR was used to detect the expression of the DcR1, DcR2, DR4 and DR5 gene.

RESULTS

All the four genes (DcR1, DcR2, DR4 and DR5) showed different methylation of promoters in TSCC, while methylation of these promoters in paired adjacent normal tissues were almost undetectable. Patients with high methylation index were diagnosed at younger age when compared with the ones with low methylation index. DcR1 and DR4 hypermethylation was correlated significantly with patients' TNM stage.

CONCLUSIONS

Methylation of DcR1, DcR2,DR4 and DR5 promoters are found in TSCC and may associate with its occurrence and development. Taking the reversibility of methylation into account,methylation is a potential targeted therapy of TSCC.

摘要

目的

舌鳞状细胞癌(TSCC)是口腔最常见的恶性肿瘤之一,近年来其发病率和死亡率不断上升。大量肿瘤抑制基因参与 TSCC 的发生,已有报道称肿瘤抑制基因的异常高甲基化可能在 TSCC 过程中发挥关键作用。本研究旨在分析 DcR1、DcR2、DR4 和 DR5 基因启动子甲基化与 TSCC 临床意义的相关性,评估 DcR1、DcR2、DR4 和 DR5 基因甲基化与舌鳞状细胞癌临床意义的相关性。

方法

采用甲基化特异性 PCR(MSP)分析 45 例 TSCC 病例 TRAIL(肿瘤坏死因子相关凋亡诱导配体)受体启动子的甲基化情况。实时 PCR 检测 DcR1、DcR2、DR4 和 DR5 基因的表达。

结果

所有四个基因(DcR1、DcR2、DR4 和 DR5)在 TSCC 中均显示出启动子的不同甲基化,而配对的相邻正常组织中这些启动子的甲基化几乎无法检测到。与低甲基化指数患者相比,高甲基化指数患者的诊断年龄较小。DcR1 和 DR4 高甲基化与患者的 TNM 分期显著相关。

结论

DcR1、DcR2、DR4 和 DR5 启动子的甲基化在 TSCC 中存在,可能与肿瘤的发生和发展有关。鉴于甲基化的可逆性,甲基化是 TSCC 潜在的靶向治疗方法。

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