Open Access

Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer

  • Authors:
    • Yuexiao Qi
    • Yuehua Wei
    • Qiaoli Wang
    • Hui Xu
    • You Wang
    • Anqi Yao
    • Hui Yang
    • Yan Gao
    • Fuxiang Zhou
  • View Affiliations

  • Published online on: September 5, 2016     https://doi.org/10.3892/ol.2016.5086
  • Pages: 3081-3088
  • Copyright: © Qi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitochondrial dysfunction is associated with pathogenic mitochondrial (mt)DNA mutations. The majority of mtDNA point mutations have a heteroplasmic status, which is defined as the coexistence of wild‑type and mutated DNA within a cell or tissue. Previous findings demonstrated that certain mtDNA heteroplasmic mutations contribute to widely spread chronic diseases, including cancer, and alterations in the heteroplasmy level are associated with the clinical phenotype and severity of cancer. In the present study, the proportions of mutant mtDNA 10398G were assessed using amplification‑refractory mutation system‑quantitative polymerase chain reaction (PCR) assay in 129 non‑small cell lung cancer (NSCLC) tissue samples. Wild‑type and mutant sequences were separately amplified using allele‑specific primers and, subsequently, the PCR products containing the mtDNA 10398 site were ligated into vectors to construct a standard plasmid DNA construct. The association between mtDNA A10398G and the prognosis of patients was analyzed by survival analysis and Cox proportional hazards model. For the patient cohort, the median follow‑up time and overall survival time were 20.6 and 26.3 months, respectively. The ratios of mutant heteroplasmy ranged between 0.31 and 97.04%. Patients with a high degree of mutant mtDNA 10398G had a significantly longer overall survival time compared with those with a low degree of mutant mtDNA 10398G (28.7 vs. 22.5 months, respectively; P<0.05). In addition, multivariate analysis demonstrated that epidermal growth factor receptor mutation status, tumor stage and the possession of a low degree of mutant 10398G were the three most independent prognostic factors. In conclusion, the present study suggests that, among NSCLC patients, there are large shifts in mutant mtDNA 10398G heteroplasmy and a low degree of mutant mtDNA 10398G heteroplasmy may be a marker of poor prognosis in patients with NSCLC.
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November-2016
Volume 12 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Qi Y, Wei Y, Wang Q, Xu H, Wang Y, Yao A, Yang H, Gao Y and Zhou F: Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer. Oncol Lett 12: 3081-3088, 2016.
APA
Qi, Y., Wei, Y., Wang, Q., Xu, H., Wang, Y., Yao, A. ... Zhou, F. (2016). Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer. Oncology Letters, 12, 3081-3088. https://doi.org/10.3892/ol.2016.5086
MLA
Qi, Y., Wei, Y., Wang, Q., Xu, H., Wang, Y., Yao, A., Yang, H., Gao, Y., Zhou, F."Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer". Oncology Letters 12.5 (2016): 3081-3088.
Chicago
Qi, Y., Wei, Y., Wang, Q., Xu, H., Wang, Y., Yao, A., Yang, H., Gao, Y., Zhou, F."Heteroplasmy of mutant mitochondrial DNA A10398G and analysis of its prognostic value in non-small cell lung cancer". Oncology Letters 12, no. 5 (2016): 3081-3088. https://doi.org/10.3892/ol.2016.5086