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Decreased copy number of mitochondrial DNA: A potential diagnostic criterion for gastric cancer

机译:线粒体DNA拷贝数减少:胃癌的潜在诊断标准

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摘要

An alteration in the mitochondrial DNA (mtDNA) copy number has been detected in numerous human cancers. However, certain changes in the mtDNA copy number that occur during the initiation and progression of gastric cancer remain undetected. In the present study, using quantitative PCR analysis, the quantitative changes in mtDNA were observed during the initiation and progression of gastric cancer. Furthermore, the possible correlation between the changes in mtDNA and the clinicopathological stage were also investigated. However, the mechanism by which the change in mtDNA copy number occurs remains to be elucidated. Epigenetic changes are believed to play a significant role in regulating the mtDNA content. In order to determine whether there is a potential correlation between DNA methylation and mtDNA regulation, in vitro demethylation experiments were performed. Tumor tissues and corresponding non-cancerous tissues were surgically resected from 76 gastric cancer patients between 2010 and 2011. The results revealed that the average relative mtDNA copy numbers were 94.71±28.11 in the cancer tissues and 111.68±21.84 in the corresponding non-cancerous tissues (P<0.01). The quantitative changes in mtDNA demonstrated a significant decrease in gastric cancer, particularly in ill-defined stage III and IV cases, but had no association with gender. The mtDNA copy numbers demonstrated a marked increase (P<0.05) following demethylation treatment. The present results indicate that the mtDNA copy number plays a significant role during the progression of colorectal cancer, particularly during the late clinicopathological stages, and that the change in the mtDNA copy number may correlate with DNA methylation.
机译:在许多人类癌症中已经检测到线粒体DNA(mtDNA)拷贝数的变化。然而,仍未发现在胃癌的发生和发展过程中发生的mtDNA拷贝数的某些变化。在本研究中,使用定量PCR分析,在胃癌的发生和发展过程中观察到了mtDNA的定量变化。此外,还研究了mtDNA变化与临床病理分期之间的可能相关性。但是,mtDNA拷贝数发生变化的机制仍有待阐明。据信表观遗传变化在调节mtDNA含量方面起着重要作用。为了确定DNA甲基化和mtDNA调控之间是否存在潜在的相关性,进行了体外脱甲基化实验。在2010年至2011年之间,通过手术切除了76例胃癌患者的肿瘤组织和相应的非癌组织。结果显示,癌组织的平均相对mtDNA拷贝数为94.71±28.11,相应的非癌组织的平均相对mtDNA拷贝数为111.68±21.84。 (P <0.01)。 mtDNA的定量变化表明胃癌明显减少,特别是在III和IV期不明确的病例中,但与性别无关。脱甲基处理后,mtDNA拷贝数显示出显着增加(P <0.05)。目前的结果表明,mtDNA拷贝数在结直肠癌的进展过程中起着重要作用,尤其是在临床病理后期,并且mtDNA拷贝数的变化可能与DNA甲基化有关。

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