Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy.
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.
Lin
Chen-Sung
CS
Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
Wang
Liang-Shun
LS
Tsai
Chun-Ming
CM
Wei
Yau-Huei
YH
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000032:analysis*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018384:Oxidative Stress; D011013:Pneumonectomy; D012189:Retrospective Studies; D016896:Treatment Outcome; D000093542:Gemcitabine
D004272:DNA, Mitochondrial; D003841:Deoxycytidine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D002945:Cisplatin; D000093542:Gemcitabine