Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy.
Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy.
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DOI：
10.1510/icvts.2008.177006
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发表时间：
2008-12-01
影响因子：
--
通讯作者：
Wei, Yau-Huei
中科院分区：
文献类型：
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作者：
Lin, Chen-Sung;Wang, Liang-Shun;Wei, Yau-Huei
癌组织中线粒体DNA（mtDNA）拷贝数的减少可能与线粒体DNA氧化损伤的减少有关，从而实现癌症永生化和进展。肺癌标本收集自29例新辅助化疗后手术切除的III期非小细胞肺癌（NSCLC）患者。通过定量实时PCR测量每个癌组织的相对mtDNA拷贝数和mtDNA氧化损伤（mtDNA中8-OHdG的形成）。7名女性和22名男性肺癌患者，平均年龄为63.5岁。术前化疗后，5例患者的肿瘤进展，13例稳定，11例部分缓解。发现低mtDNA拷贝数（P=0.089）和低程度的mtDNA氧化损伤（P=0.036）与肿瘤进展相关。线粒体DNA拷贝数与线粒体DNA氧化损伤程度显著相关（P=0.031）。化疗后晚期非小细胞肺癌患者线粒体DNA拷贝数和氧化损伤均较化疗前降低。这一发现表明，mtDNA含量的降低可能导致癌细胞中线粒体密度的降低，从而导致内源性ROS产生的减少和ROS触发的DNA损伤的减少，以实现永生化。
The decrease in the copy number of mitochondrial DNA (mtDNA) in cancer tissues might be associated with a decrease in oxidative mtDNA damage to achieve cancer immortalization and progression. Lung cancer specimens were collected from 29 patients with stage III non-small cell lung cancer (NSCLC) after neoadjuvant chemotherapy followed by surgical resection. The relative mtDNA copy number and the oxidative mtDNA damage (formation of 8-OHdG in mtDNA) of each cancer tissue were measured by quantitative real-time PCR. Seven female and 22 male lung cancer patients, with a mean age of 63.5 years were evaluated. Tumors of five patients became progressive, 13 stable, and 11 partially responsive after preoperative chemotherapy. Low mtDNA copy number (P=0.089) and low degree of oxidative mtDNA damage (P=0.036) were found to associate with tumor progression. Moreover, mtDNA copy number was significantly related to the degree of oxidative mtDNA damage (P=0.031). The mtDNA copy number and oxidative mtDNA damage were lower in advanced NSCLC after chemotherapy. This finding suggests that a decrease in the content of mtDNA may result in a decrease of mitochondrial density in cancer cells, which leads to a decrease of endogenous ROS production and reduction of ROS-triggered DNA damage to achieve immortalization.