Hypermethylation and Expression Silencing of PDCD4 Gene in Hepatocellular Carcinoma: A Consort Study.
Hypermethylation and Expression Silencing of PDCD4 Gene in Hepatocellular Carcinoma: A Consort Study.
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DOI：
10.1097/md.0000000000002729
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发表时间：
2016-02
期刊：
影响因子：
1.6
通讯作者：
Lai K
中科院分区：
文献类型：
--
作者：
Ding X;Cheng X;Gong M;Chen X;Yin F;Lai K
程序性细胞死亡4（PDCD4）是一种新型肿瘤抑制因子，参与癌症的发生和进展。然而，PDCD4在肝细胞癌（HCC）中的作用尚未见报道。本研究的目的是探讨PDCD4失活在HCC中的分子机制及其临床意义。通过定量实时聚合酶链反应（qRT-PCR）分析HCC组织和邻近非肿瘤组织中PDCD4的mRNA水平。进行亚硫酸氢盐测序PCR以确定PDCD4启动子的甲基化状态。进一步分析PDCD4 mRNA表达水平和甲基化水平与临床病理特征。 qRT-PCR分析显示，肿瘤组织中PDCD4 mRNA水平较邻近非肿瘤组织显着降低。 HCC组织中PDCD4启动子甲基化率显着高于癌旁非肿瘤组织。 PDCD4 mRNA水平和启动子甲基化水平均与HCC的转移和分化程度具有统计学相关性。此外，PDCD4 高甲基化、mRNA 水平和总生存期 (OS) 之间的相关性具有统计学意义。我们的研究结果表明，PDCD4可能是HCC中新的抑癌基因候选基因，启动子高甲基化是其下调的重要机制，也是HCC OS的良好预测因子。
Programmed cell death 4 (PDCD4) is a novel tumor suppressor, which is involved in the initiation and progression of cancers. However, the role of PDCD4 in hepatocellular carcinoma (HCC) has not been reported. The aim of this study was to investigate the molecular mechanism and clinical significance of PDCD4 inactivation in HCC. The mRNA levels of PDCD4 in HCC tissues and adjacent nontumor tissues were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Bisulfite sequencing PCR was performed to determine the methylation status of PDCD4 promoter. Furthermore, the mRNA expression level and the methylated level of PDCD4 were analyzed with the clinical and pathological characteristics. qRT-PCR analysis showed that PDCD4 mRNA levels in tumor tissues were significantly decreased compared with that in adjacent nontumor tissues. The methylation rate of PDCD4 promoter was significantly higher in HCC tissues than that in adjacent nontumor tissues. PDCD4 mRNA levels and promoter methylation levels were both statistically correlated with metastasis and the degree of differentiation in HCC. In addition, the correlation between PDCD4 hypermethylation, mRNA levels, and overall survival (OS) was statistically significant. Our results indicated that PDCD4 may be a novel candidate of tumor suppressor gene in HCC, and that promoter hypermethylation is an important mechanism for its downregulation and is also a good predictor of OS for HCC.