Reduced expression of DENND2D through promoter hypermethylation is an adverse prognostic factor in squamous cell carcinoma of the esophagus
Reduced expression of DENND2D through promoter hypermethylation is an adverse prognostic factor in squamous cell carcinoma of the esophagus
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DOI：
10.3892/or.2013.2901
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发表时间：
2014-02-01
期刊：
影响因子：
4.2
通讯作者：
Kodera, Yasuhiro
中科院分区：
文献类型：
--
作者：
Hibino, Soki;Kanda, Mitsuro;Kodera, Yasuhiro
食道癌在全球癌症死亡率中居第六位，食管鳞癌患者预后差，5年生存率不到10%。目前迫切需要阐明食道癌发生和发展的机制，以开发治疗和预后生物标志物的靶点。本研究通过研究Rab GTP酶的调控基因2D(DENND2D)在正常细胞和肿瘤细胞中的差异表达及其调控机制，探讨其作为食管鳞癌抑癌基因的可能性。采用实时定量逆转录-聚合酶链式反应技术检测食管癌细胞株和手术标本中DENND2D基因的表达水平，并探讨其与临床病理因素的关系。免疫组织化学方法检测DENND2D的表达和分布。DNA甲基化分析以确定DENND2D在ESCC中表达的调控机制。DENND2D在8/9 ESCC细胞系和59/65例手术标本中表达降低，癌组织的平均表达水平显著低于相应的正常组织(P
Esophageal cancer ranks sixth in cancer mortality worldwide and patients with esophageal squamous cell carcinoma (ESCC) have a poor prognosis with a 5-year survival rate of less than 10%. Elucidation of the mechanisms of carcinogenesis and tumor progression in esophageal cancer is urgently required to develop targets for therapy and prognostic biomarkers. In the present study, the expression and regulatory mechanism of the differentially expressed in normal and neoplastic cells domain containing 2D (DENND2D), which is a regulator of Rab GTPases, were investigated to explore its potential as a tumor suppressor gene for ESCC. The level of DENND2D mRNA expression in ESCC cell lines and surgical specimens was determined using a quantitative real-time reverse transcription-polymerase chain reaction assay, and the relationship between the expression levels of DENND2D mRNA and clinicopathological factors was evaluated. The expression and distribution of DENND2D were determined using immunohistochemistry. DNA methylation analysis was performed to determine the regulatory mechanism of DENND2D expression in ESCC. The level of DENND2D mRNA expression was reduced in 8/9 ESCC cell lines and in 59/65 surgical specimens, and the mean expression levels were significantly lower in cancerous tissues compared to corresponding normal tissues (P