Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma.
Expression pattern and clinical significance of DNA methyltransferase 3B variants in gastric carcinoma.
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DOI：
10.3892/or_00000703
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发表时间：
2010-03
期刊：
影响因子：
4.2
通讯作者：
X. Su;Chengyu Lv;Fengchang Qiao;X. Qiu;Wen-sheng Huang;Qingxiang Wu;Zhujiang Zhao;H. Fan
中科院分区：
文献类型：
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作者：
X. Su;Chengyu Lv;Fengchang Qiao;X. Qiu;Wen-sheng Huang;Qingxiang Wu;Zhujiang Zhao;H. Fan
本研究旨在检测DNA甲基转移酶3B （DNMT3B）变异在原发性胃癌（GC）中的表达模式，探讨DNMT3B变异在胃癌发生中的临床意义。设计了特定的聚合酶链反应（PCR）引物集，根据DNMT3B的剪接模式区分个体DNMT3B变异。采用实时荧光定量RT-PCR技术检测DNMT3B在胃癌组织、正常胃黏膜和胃癌细胞株中的表达水平。通过观察不同变异在肿瘤中的表达水平，分析DNMT3B变异的表达模式与相应临床信息的关系。上述结果表明，DNMT3B过表达与胃癌晚期侵袭（P=0.029）和肠道类型（P=0.012）有关。DNMT3B3在正常组织中的表达高于肿瘤组织（P=0.033）。相比之下，只有18%、32%和35%的患者肿瘤分别过表达DNMT3B1、DNMT3B4和DNMT3B5。在考虑环境因素（幽门螺杆菌、eb病毒感染）的情况下，幽门螺杆菌感染使肿瘤中DNMT3B1和DNMT3B3变异体升高，而在肿瘤和非癌组织中DNMT3B4变异体升高。我们的研究结果表明，DNMT3B3的表达是正常胃粘膜的主要剪接变体，并可能受到幽门螺杆菌感染的影响。DNMT3B变异的升高可能影响胃癌的进展，可能是该疾病的一个强有力的指标。
The aim of this study was to detect the expression pattern of DNA methyltransferase 3B (DNMT3B) variants in primary gastric cancer (GC) and to explore the clinical significance of DNMT3B variants in gastric carcinogenesis. Specific polymerase chain reaction (PCR) primer sets were designed to distinguish individual DNMT3B variants according to their splicing patterns. Expression levels of DNMT3B variants were assessed by quantitative real-time RT-PCR in gastric cancer tissue, normal gastric mucosae and GC cell lines. The relationship between the expression patterns of the DNMT3B variants and corresponding clinical information was analyzed by observing the expression levels of different variants in the tumors. These results demonstrate that DNMT3B overexpression is related to late phase invasion (P=0.029) and intestinal type (P=0.012) in GC. DNMT3B3 expression was higher in normal tissue, compared to tumor tissue (P=0.033). In contrast, only 18, 32 and 35% of the patient tumors overexpressed DNMT3B1, DNMT3B4 and DNMT3B5, respectively. While taking into account environmental factors (H. pylori, Epstein-Barr virus infection), H. pylori infection elevated DNMT3B1 and DNMT3B3 variants in tumors, while increasing DNMT3B4 in both tumor and non-cancerous tissues. Our findings indicated that the expression of DNMT3B3 is the major splice variant in normal gastric mucosae and may be affected by H. pylori infection. Elevated DNMT3B variants may influence the progression of gastric cancer and may possibly be a powerful indicator for the disease.