title: Low copy number and low oxidative damage of mitochondrial DNA are associated with tumor progression in lung cancer tissues after neoadjuvant chemotherapy.
abstract: 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.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei 112, Taiwan.
authors.forename: Chen-Sung
authors.initials: CS
authors.lastname: Lin
authors.forename: Liang-Shun
authors.initials: LS
authors.lastname: Wang
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Tsai
authors.forename: Yau-Huei
authors.initials: YH
authors.lastname: Wei
mesh_terms: 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
chemical_list: D004272:DNA, Mitochondrial; D003841:Deoxycytidine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D002945:Cisplatin; D000093542:Gemcitabine