Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy
Chen-Sung Lin 1,
Liang-Shun Wang 2,
Chun-Ming Tsai 3,
Yau-Huei Wei 1*
1 National Yang-Ming University, Taipei, Taiwan
2 En Chu Kong Hospital, Taipei, Taiwan
3 Taipei Veterans General Hospital, Taiwan
* To whom correspondence should be addressed. E-mail: d49424006{at}ym.edu.tw.
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Abstract |
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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 5 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, the 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. Keywords: 8-OHdG; mtDNA copy number; NSCLC; Oxidative damage; ROS
